[DB] N-(1-(4-'G'-2,5-Dimethoxyphenyl)propan-2-yl)-2,2,2-trifluoroacetamide to 1-(4-'G'-2,5-Dimethoxy

Query Query F

O

F

H N

H 2N

F

1. Query

Results

Date

30 reactions in Reaxys

2018-07-18 06h:44m:55s (UTC)

O

O G O

G O

Search as: Product, As drawn, No mixtures ))

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F

F

O

F

O

HN H 2N

O

F O

F

O

Rx-ID: 2598444 View in Reaxys 1/30 Yield

Conditions & References

86 %

With potassium hydroxide in water, isopropyl alcohol, Time= 0.5h, T= 45 °C Gerdes, John M.; Mathis, Chester A.; Shulgin, Alexander T.; Tetrahedron Letters; vol. 29; nb. 50; (1988); p. 6537 - 6540 View in Reaxys F

F

O

F

O

HN H 2N

O

F O

OH

O

Rx-ID: 21572879 View in Reaxys 2/30 Yield

Conditions & References Reaction Steps: 3 1: 96 percent / pyridine / 12 h / 0 °C 2: 55 percent / tetrabutylammonium fluoride / tetrahydrofuran / 0.5 h / Heating 3: 86 percent / KOH / H2O; propan-2-ol / 0.5 h / 45 °C With pyridine, potassium hydroxide, tetrabutyl ammonium fluoride in tetrahydrofuran, water, isopropyl alcohol Gerdes, John M.; Mathis, Chester A.; Shulgin, Alexander T.; Tetrahedron Letters; vol. 29; nb. 50; (1988); p. 6537 - 6540 View in Reaxys

O

O H 2N

F HN

F

O S F

O

O

F

O O

O

Rx-ID: 21578275 View in Reaxys 3/30 Yield

Conditions & References Reaction Steps: 2 1: 55 percent / tetrabutylammonium fluoride / tetrahydrofuran / 0.5 h / Heating 2: 86 percent / KOH / H2O; propan-2-ol / 0.5 h / 45 °C With potassium hydroxide, tetrabutyl ammonium fluoride in tetrahydrofuran, water, isopropyl alcohol Gerdes, John M.; Mathis, Chester A.; Shulgin, Alexander T.; Tetrahedron Letters; vol. 29; nb. 50; (1988); p. 6537 - 6540 View in Reaxys

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F

F

O

F

O

HN H 2N

O

O

O

O

O

Rx-ID: 2234994 View in Reaxys 4/30 Yield

Conditions & References With sodium hydroxide in methanol, water, Time= 2.5h, Heating, Yield given Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys

F F O

H 2N

F

O HN O

O O O O

Rx-ID: 25847552 View in Reaxys 5/30 Yield

Conditions & References 3 :N-{(R)-2-[2,5-Dimethoxy-4-(2-methoxy-ethyl)-phenyl]-1-methyl-ethyl}-2,2,2-trifluoro-acetamide (0.40 g, 1.14 mmol) prepared above was dissolved in methanol (25 mL) and a 5.0 N solution of sodium hydroxide (15 mL) was added.

The solution was stirred overnight at room temperature.

Solvent was removed under reduced pressure and product was extracted with dichloromethane, dried (MgSO4), and concentrated to yield a white solid which was dissolved in anhydrous ethyl ether the free base was transformed to its hydrochloride correspondent (method B) to yield a white solid (0.23 g, 70percent).

1H NMR (DMSO, d ): δ ppm 1.12 (d, 3H), 2.68-2.71 (m, 1H), 2.77-2.79 (m, 2H), 2.87-2.90 (m, 1H), 3.25 (s, 3H), 3.4 (m, 1H), 6 3.47-3.49 (m, 2H), 3.74 (m, 6H), 6.80 (s, 1H), 6.87 (s, 1H), 7.98 (s, 3H); LCMS (+APCI) m/z 254 (M+H). CHN analysis for C14H23NO3+1HCl: Calculated: C 58.02, H 8.35, N 4.83; Found: C 58.21, H 8.37, N 4.83.

With sodium hydroxide, water in methanol, T= 20 °C Patent; Alcon, Inc.; US2007/72920; (2007); (A1) English View in Reaxys

O

O F

H 2N

HN

F

F F

F

O F O

F

O

F

F

Rx-ID: 4101692 View in Reaxys 6/30 Yield

Conditions & References With potassium hydroxide in isopropyl alcohol, Time= 3h, Ambient temperature

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Nichols, David E.; Frescas, Stewart; Marona-Lewicka, Danuta; Huang, Xuemei; Roth, Bryan L.; et al.; Journal of Medicinal Chemistry; vol. 37; nb. 25; (1994); p. 4346 - 4351 View in Reaxys F

F

O

F

O HN

H 2N

O

F

O

F

F

I O

Rx-ID: 18107345 View in Reaxys 7/30 Yield

Conditions & References Reaction Steps: 2 1: 1.) CuI, KF / 1.) DMF, 120 deg C, 2.) DMF, 120 deg C, 4 h 2: 2N KOH / propan-2-ol / 3 h / Ambient temperature With potassium fluoride, potassium hydroxide, copper(l) iodide in isopropyl alcohol Nichols, David E.; Frescas, Stewart; Marona-Lewicka, Danuta; Huang, Xuemei; Roth, Bryan L.; et al.; Journal of Medicinal Chemistry; vol. 37; nb. 25; (1994); p. 4346 - 4351 View in Reaxys

F F O

H 2N

F

O HN O

O

O

O

O

Rx-ID: 25847563 View in Reaxys 8/30 Yield

Conditions & References 6 :N-{(R)-2-[2,5-Dimethoxy-4-(3-methoxy-propyl)-phenyl]-1-methyl-ethyl}-2,2,2-trifluoro-acetamide (0.20 g, 0.55 mmol) was dissolved in methanol (25 mL) in a 250 mL round bottom flask.

Next, a 15percent NaOH solution (15 mL) was added.

The reaction was stirred at room temperature overnight.

Solvent was removed and product was extracted with DCM, dried with anhydrous MgSO4, and concentrated to yield a white solid which was dissolved in anhydrous ethyl ether.

To this solution was added 1.0M solution of hydrogen chloride in ethyl ether.

The precipitate was collected by vacuum filtration to give a white solid: 0.080 g (54percent).

1H-NMR (400 MHz, DMSO, d ): δ ppm 1.12 (m, 3H), 1.72-1.76 (m, 2H), 2.56-2.58 (m, 2H), 2.67-2.70 (m, 1H), 2.87-2.88 (m, 6 1H), 3.32 (m, 2H), 3.38 (m, 1H), 3.74 (s, 6H), 6.80 (s, 2H), 8.02 (bs, 3H). MS (APCI) m/z 268 (M+H). CHN analysis for C15H25NO3.HCl: Calculated: C 59.30, H 8.63, N 4.61; Found: C 59.12, H 8.57, N 4.57.

With sodium hydroxide, water in methanol, T= 20 °C Patent; Alcon, Inc.; US2007/72920; (2007); (A1) English View in Reaxys

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F

F

O

F

O

HN H 2N

O

O

O

Rx-ID: 2233714 View in Reaxys 9/30 Yield

Conditions & References With sodium hydroxide in methanol, Time= 2.5h, Heating, Yield given Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys F

F

O

F

O HN

H 2N

O

O

O

O

Rx-ID: 21961333 View in Reaxys 10/30 Yield

Conditions & References Reaction Steps: 2 1: 66 percent / H2, 60percent aq. HClO4 / 10percent Pd/C / acetic acid / 6 h 2: 15percent aq. NaOH / methanol / 2.5 h / Heating With sodium hydroxide, perchloric acid, hydrogen, 10 wt. % palladium on activated carbon in methanol, acetic acid Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys

F F O

H 2N

F

O

HN O

O O

O

O O

O

Rx-ID: 25847553 View in Reaxys 11/30 Yield

Conditions & References 1 :To a solution of {2,5-dimethoxy-4-[2-(2,2,2-trifluoro-acetylamino)-propyl]-phenyl}-acetic acid ethyl ester (0.50 g, 1.3 mmol) in 50 mL of a mixture of methanol and water (4:1 V/V) was added 10 mL of a 5.0 N solution of sodium hydroxide.

The reaction mixture was allowed to stir for 12 h, and then concentrated under reduced pressure.

The residue was dissolved in 50 mL of ethanol and acidified by addition of 5 mL of sulfuric acid.

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The reaction mixture was warmed at reflux for 4 h, cooled and concentrated under reduced pressure.

The residue was partitioned in a mixture of water and dichloromethane, and then neutralized by addition of a saturated solution of sodium bicarbonate.

The organic layer was separated, dried (anhydrous MgSO4), and the solvent was removed under reduced pressure The residue was dissolved in diethyl ether.

To this solution was added 1.0 N solution of hydrogen chloride in diethyl ether.

The solid that formed was collected by filtration. 1H NMR (DMSO, d6): δ ppm 1.10 (d, 3H), 1.15 (m, 3H), 2.69 (dd, 1H), 2.90 (dd, 1H), 3.37 (m, 1H), 3.54 (s, 2H), 3.67 (s, 3H), 3.71 (s, 3H), 4.05 (m, 2H), 6.82 (s, 1H), 6.87 (s, 1H), 8.11 (bs, 3H). CHN analysis for C15H23NO4+1.0 HCl: Calculated C 56.69, H 7.61, N 4.41; Found C 56.52, H 7.68, N 4.43 Stage 1: With sodium hydroxide, water in methanol, Time= 12h Stage 2: With sulfuric acid in ethanol, Time= 4h, Heating / reflux Patent; Alcon, Inc.; US2007/72920; (2007); (A1) English View in Reaxys

F F O

H 2N

F

O

HN O

S

S

O

O

Rx-ID: 25847562 View in Reaxys 12/30 Yield

Conditions & References 5 :N-{(R)-2-[2,5-Dimethoxy-4-(3-methylsulfanyl-propyl)-phenyl]-1-methyl-ethyl}-2,2,2-trifluoro-acetamide (0.10 g, 0.40 mmol) was dissolved in methanol (20 mL). Next, a 15percent NaOH solution (15 mL) was added. The reaction was stirred at room temperature overnight. Solvent was removed and product was extracted with DCM. The organic extracts were dried with anhydrous MgSO4, and concentrated to yield an off-white solid which was dissolved in anhydrous ethyl ether. To this solution was added 1.0M solution of hydrogen chloride in ethyl ether. The precipitate was collected by vacuum filtration to give a tan solid: 0.041 g (55percent). 1H NMR (600 MHz, DMSO, d6): δ ppm 1.12 (m, 3H), 1.76-1.80 (m, 2H), 2.05 (s, 3H), 2.46-2.48 (m, 2H), 2.60-2.62 (m, 2H), 2.64 (m, 1H), 2.70 (m, 1H), 3.4 (m, 1H), 3.74 (s, 6H), 6.80-6.82 (m, 2H), 7.99 (bs, 3H). MS (APCI) m/z 284 (M+H). CHN analysis for C15H25NO2.1.0 HCl+0.6 H2O: Calculated C 54.48, H 8.29, N 4.24; Found C 54.46, H 8.02, N 4.17.

With sodium hydroxide, water in methanol, T= 20 °C Patent; Alcon, Inc.; US2007/72920; (2007); (A1) English View in Reaxys

F

O

F H N

O H 2N

F O

O

O

Rx-ID: 2235675 View in Reaxys 13/30 Yield

Conditions & References With sodium hydroxide in methanol, Time= 2.5h, Heating, Yield given Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys

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O

F

F

O

H N

H 2N

F O

O

O

O

Rx-ID: 21961836 View in Reaxys 14/30 Yield

Conditions & References Reaction Steps: 2 1: 61 percent / H2, 60percent aq. HClO4 / 10percent Pd/C / acetic acid / 6 h 2: 15percent aq. NaOH / methanol / 2.5 h / Heating With sodium hydroxide, perchloric acid, hydrogen, 10 wt. % palladium on activated carbon in methanol, acetic acid Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys

F F O

H 2N

F

O

HN O

O

O

Rx-ID: 25847569 View in Reaxys 15/30 Yield

Conditions & References 17 :N-[(R)-2-(4-Benzyl-2,5-dimethoxy-phenyl)-1-methyl-ethyl]-2,2,2-trifluoro-acetamide (0.21 g, 0.55 mmol) was dissolved in methanol (25 mL).

Next, a 15percent NaOH solution (15 mL) was added.

The reaction was stirred at room temperature overnight.

Solvent was removed and product was extracted with DCM, dried with anhydrous MgSO4, and concentrated to yield a white solid which was dissolved in anhydrous ethyl ether.

To this solution was added 1.0M solution of hydrogen chloride in ethyl ether.

The precipitate that formed was collected by vacuum filtration to give a white solid: 0.11 g. 1H-NMR (400 MHz, DMSO, d6): δ ppm 1.12 (m, 3H), 2.67-2.73 (m, 1H), 2.86-2.91 (m, 1H), 3.37-3.40 (m, 1H), 3.70 (s, 3H), 3.74 (s, 3H), 3.88 (s, 2H), 6.83 (s, 1H), 6.87 (s, 1H), 7.14-7.28 (m, 5H), 7.95 (bs, 3H). MS (APCI) m/z 286 (M+H). CHN analysis for C18H23NO2.1.0HCl.0.2H2O: Calculated: C 66.43, H 7.56, N 4.30; Found: C 66.40, H 7.43, N 4.29.

With sodium hydroxide, water in methanol, T= 20 °C Patent; Alcon, Inc.; US2007/72920; (2007); (A1) English View in Reaxys

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F F O

H 2N O

F HN O

O

H N OH

O O O O

N N

O

Rx-ID: 29860229 View in Reaxys 16/30 Yield

Conditions & References 2 :To a cold suspension (ice bath) of NaH (0.15 g, 4.0 mmol) in 50 mL of THF was added N-hydroxy acetamide.

The heterogeneous reaction mixture was stirred at 60° C. for 30 min, and then {2,5-dimethoxy-4-[2-(2,2,2-trifluoro-acetylamino)-propyl]-phenyl}-acetic acid ethyl ester (0.5 g, 1.33 mmol) was added.

The reaction mixture was stirred at reflux temperature for an additional 3 h, and allowed to cool to room temperature and partitioned in a mixture of dichloromethane/water.

The organic layer was separated, and diluted with aqueous 1 N HCl. The solution was separated, neutralized by addition of a saturated bicarbonate solution, and extracted with DCM. The organic layer was dried (anhydrous MgSO4), and concentrated under reduced pressure.

The residue was converted to the hydrochloride salt by method B, and the solid that formed was recrystallized from methanolether to give 0.10 g of the desired material. 1H NMR (CD3OD): δ ppm 1.32 (d, 3H), 2.33 (s, 3H), 2.93 (m, 2H), 3.60 (m, 1H), 3.77 (s, 3H), 3.85 (s, 3H), 4.22 (s, 2H), 6.87 (s, 1H), 7.08 (s, 1H), LCMS (+APCI) m/z 292 (M+H. CHN analysis calculated for C15H21N3O3.HCl: Calculated C 54.96, H 6.76, N 12.82, found C 54.96, H 6.75, N 12.76 Stage 1: With sodium hydride in tetrahydrofuran, Time= 0.5h, T= 0 - 60 °C Stage 2: in tetrahydrofuran, Time= 3h, Heating / reflux Patent; Alcon, Inc.; US2007/72920; (2007); (A1) English View in Reaxys

F F O H 2N

F

O

HN O HS NH 2

Cl

H

O S

N

O O

O

Rx-ID: 29860226 View in Reaxys 17/30 Yield

Conditions & References 10 :To a solution of cysteamine hydrochloride (0.8 g, 7.04 mmol) in toluene (60 mL) was added 1.0 M solution of i-Bu3Al (19.89 mL, 19.89 mmol) in toluene under nitrogen.

The mixture was stirred for at reflux for 1 h.

To this solution was added {2,5-dimethoxy-4-[2-(2,2,2-trifluoro-acetylamino)-propyl]-phenyl}-acetic acid ethyl ester (3.0 g, 7.95 mmol), and the mixture was warmed at reflux for 2 h, cooled to room temperature, quenched by dropwise addition of 5 mL of methanol, and stirred for 10 min.

To this solution was added 20 mL of saturated Rochelle's salts solution, 20 ml of saturated solution of Na2CO3, and 20 mL of saturated NaCl. To this solution was added ethyl acetate (100 mL), and the mixture was stirred vigorously for 15 min.

The organic layer was separated, dried (anhydrous MgSO4), and the solvent was removed under reduced pressure.

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The residue was hydrolyzed by method A, and the free base was converted to its hydrochloride salt by method B. Recrystallization in methanol-diethyl ether gave 240 mg of an off white solid. 1H NMR (DMSO, d6): δ 1.13 (d, 3H), 2.71-2.96 (dd, 2H), 3.5 (m, 1H), 3.57 (m, 2H), 3.75-377 (2s, 6H), 4.06 (s, 2H), 4.28 (m, 2H), 6.93 (s, 1H), 7.01 (s, 1H), 8.14 (bs, 3H).

LCMS (+APCI) m/z 295 (M+H). CHN analysis calculated for C15H22N2O2S+2.0 HCl+0.6 H2O: Calculated C 47.64, H 6.72, N 7.41, found C 47.51, H 6.50, N 7.33 Stage 1: With aluminium isobutyl hydride in toluene, Time= 1h, Heating / reflux Stage 2: in toluene, Time= 2h, Heating / reflux Stage 3: With methanol in toluene, Time= 0.166667h Patent; Alcon, Inc.; US2007/72920; (2007); (A1) English View in Reaxys F

F

O

F

O HN

H 2N

O

O

O

Rx-ID: 8723434 View in Reaxys 18/30 Yield

Conditions & References With sodium hydroxide in methanol, Time= 2h, Heating, Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p.

3074 - 3084 View in Reaxys

F

O

F

O

H N

H 2N

F O

O

O

O

Rx-ID: 15619682 View in Reaxys 19/30 Yield

Conditions & References Reaction Steps: 2 1: 47 percent / H2; AcOH; 70 percent HClO4 / 10 percent Pd/C / 6 h / 3102.89 Torr 2: 15 percent aq. NaOH / methanol / 2 h / Heating With sodium hydroxide, perchloric acid, hydrogen, acetic acid, 10 wt. % palladium on activated carbon in methanol, 1: Reduction / 2: Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p.

3074 - 3084 View in Reaxys

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F F O

H 2N

F

O HN O

O S

O

O S

O

Rx-ID: 25847566 View in Reaxys 20/30 Yield

Conditions & References 7 :N-{(R)-2-[2,5-Dimethoxy-4-(2-methoxymethylsulfanyl-ethyl)-phenyl]-1-methyl-ethyl}-2,2,2-trifluoro-acetamide (0.30 g, 0.76 mmol) was dissolved in methanol (25 mL).

Next, a 15percent NaOH solution (15 mL) was added.

The reaction was stirred at room temperature overnight.

Methanol was removed and the product was extracted with DCM, dried with MgSO4, and concentrated to yield a off-white solid which was dissolved in anhydrous ethyl ether.

To this solution was added 1.0M solution of hydrogen chloride in ethyl ether dropwise until no further formation of precipitate.

Ether was evaporated to yield a tan solid: 0.127 g (56percent).

1H NMR (400 MHz, DMSO, d ): δ 1.12 (m, 3H), 2.67-2.82 (m, 5H), 2.89-2.93 (m, 1H), 3.4 (s, 1H), 3.75 (s, 6H), 4.67 (s, 2H), 6 6.81 (s, 1H), 6.87 (s, 1H), 8.09 (bs, 3H). MS (APCI) m/z 300 (M+H). CHN analysis for C15H25NO3S.1.0 HCl: Calculated: C 53.64, H 7.80, N 4.17; Found: C 53.64, H 7.86, N 4.17.

With sodium hydroxide, water in methanol, T= 20 °C Patent; Alcon, Inc.; US2007/72920; (2007); (A1) English View in Reaxys F

F

O

F

O

HN O

H 2N

O

O

Rx-ID: 2234823 View in Reaxys 21/30 Yield

Conditions & References With sodium hydroxide in methanol, Time= 2.5h, Heating, Yield given Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys

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F

F

O

F

O

HN H 2N

O

O

O

O

Rx-ID: 21961973 View in Reaxys 22/30 Yield

Conditions & References Reaction Steps: 2 1: 56 percent / H2, 60percent aq. HClO4 / 10percent Pd/C / acetic acid / 6 h 2: 15percent aq. NaOH / methanol / 2.5 h / Heating With sodium hydroxide, perchloric acid, hydrogen, 10 wt. % palladium on activated carbon in methanol, acetic acid Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys F

F

O

F

O

HN H 2N

O

O

O

Rx-ID: 2237184 View in Reaxys 23/30 Yield

Conditions & References With sodium hydroxide in methanol, Time= 2.5h, Heating, Yield given Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys

F

O

O

F H N

H 2N

F O

O

O

O

Rx-ID: 21962704 View in Reaxys 24/30 Yield

Conditions & References Reaction Steps: 2 1: 63 percent / H2, 60percent aq. HClO4 / 10percent Pd/C / acetic acid / 6 h 2: 15percent aq. NaOH / methanol / 2.5 h / Heating With sodium hydroxide, perchloric acid, hydrogen, 10 wt. % palladium on activated carbon in methanol, acetic acid Seggel; Yousif; Lyon; Titeler; Roth; Suba; Glennon; Journal of Medicinal Chemistry; vol. 33; nb. 3; (1990); p. 1032 - 1036 View in Reaxys

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F

F

O

F

O

HN

H 2N

O

O

O

Rx-ID: 8725141 View in Reaxys 25/30 Yield

Conditions & References

18 %

With sodium hydroxide in methanol, Time= 2h, Heating, Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p.

3074 - 3084 View in Reaxys F

F

O

F

O

HN

H 2N O

O I O

Rx-ID: 15596554 View in Reaxys 26/30 Yield

Conditions & References Reaction Steps: 3 1: 50 percent / pyridine / 120 °C 2: 46 percent / H2 / 10 percent Pd/C / methanol / 4 h / 2068.59 Torr 3: 18 percent / 15 percent aq. NaOH / methanol / 2 h / Heating With pyridine, sodium hydroxide, hydrogen, 10 wt. % palladium on activated carbon in methanol, 1: Substitution / 2: Catalytic hydrogenation / 3: Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p.

3074 - 3084 View in Reaxys

F

O

F H N

O

F

H 2N

O

O

O

Rx-ID: 15620544 View in Reaxys 27/30 Yield

Conditions & References Reaction Steps: 2 1: 46 percent / H2 / 10 percent Pd/C / methanol / 4 h / 2068.59 Torr

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2: 18 percent / 15 percent aq. NaOH / methanol / 2 h / Heating With sodium hydroxide, hydrogen, 10 wt. % palladium on activated carbon in methanol, 1: Catalytic hydrogenation / 2: Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p.

3074 - 3084 View in Reaxys F

F

O

F

O

HN H 2N

O

O

O

O

O

Rx-ID: 8725810 View in Reaxys 28/30 Yield

Conditions & References With methanol, sodium hydroxide, Time= 2h, Heating, Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p.

3074 - 3084 View in Reaxys

F

O

F

O

H N

O

H 2N

O

F O

O

O

O

Rx-ID: 15621512 View in Reaxys 29/30 Yield

Conditions & References Reaction Steps: 2 1: H2; AcOH; 70 percent HClO4 / 10 percent Pd/C / 6 h / 3102.89 Torr 2: 15 percent NaOH; MeOH / 2 h / Heating With methanol, sodium hydroxide, perchloric acid, hydrogen, acetic acid, 10 wt. % palladium on activated carbon, 1: Reduction / 2: Hydrolysis Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p.

3074 - 3084 View in Reaxys

F

O

O

F H N

H 2N

Cl

Cl

F O

O

O

O

Rx-ID: 8725706 View in Reaxys 30/30 Yield 59 %

Conditions & References Stage 1: With potassium hydroxide, hydrazine hydrate in ethylene glycol, Time= 2h, T= 150 °C , Wolff-Kishner reduction Stage 2: With water in methanol, Heating, Hydrolysis

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Dowd; Herrick-Davis; Egan; DuPre; Smith; Teitler; Glennon; Journal of Medicinal Chemistry; vol. 43; nb. 16; (2000); p.

3074 - 3084 View in Reaxys

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