1-(3-Methoxyphenyl)cyclohexan-1-amine (3-MeO-PCA) [C13H19NO] [CAS 125802-07-5; InChIKey HCAW

1-(3-Methoxyphenyl)cyclohexan-1-amine (3-MeO-PCA) [C13H19NO]

Query Query

1. Query O

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Date

6 reactions in Reaxys

2018-07-31 10h:55m:13s (UTC)

H 2N

Search as: Product, As drawn, No mixtures ) AND (IDE.RN='125802-07-5') AND (IDE.INCHI='HCAWFOVQBDALEZUHFFFAOYSA-N') NOT (RX.RXRN=3650932))

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1-(3-Methoxyphenyl)cyclohexan-1-amine (3-MeO-PCA) [C13H19NO]

O

N N

O

H 2N

N

Rx-ID: 2299720 View in Reaxys 1/6 Yield

Conditions & References

63 %

F41 : Description F41; {1-13-(METHYLOXY) PHENYL] CYCLOHEXYL} amine (F41) To a solution of 1- (1-azidocyclohexyl)-3- (methyloxy) benzene (D315) (2.78 g, 12.0 mmol, 1 equiv) in THF (20 ml) at room temperature was added LiAIH4 (1 M in THF, 36 ML, 36 mmol, 3 equiv) and the resulting mixture was stirred at this temperature for 4 h. The mixture was then carefully quenched with a 1 N aqueous NAOH solution (6 ml, 60 mmol, 1 equiv) then H2O. The mixture was filtered through a pad of celite then acidified with a 2N aqueous HCI solution (50 ML). The two layers were separated and the pH of the aqueous phase adjusted to 9 using a 2N aqueous NAOH solution. The aqueous phase was extracted three times with ET2O and the combined organic phase were dried over MGS04 then concentrated in vacuo to give {1- [3- (METHYLOXY) PHENYL] CYCLOHEXYL} amine (F41) (1.55 g, 63percent) as a clear oil which was used in the next step without further purification. [M+H] + = 189.0, RT = 1.90 min.

Stage 1: With lithium aluminium tetrahydride in tetrahydrofuran, Time= 4h, T= 20 °C Stage 2: With sodium hydroxide, water in tetrahydrofuran Stage 3: With hydrogenchloride in tetrahydrofuran, water Patent; GLAXO GROUP LIMITED; WO2004/50619; (2004); (A1) English View in Reaxys With lithium aluminium tetrahydride in diethyl ether, Time= 3h, Yield given Thurkauf, Andrew; Costa, Brian de; Yamaguchi, Shun-ichi; Mattson, Mariena V.; Jacobson, Arthur E.; et al.; Journal of Medicinal Chemistry; vol. 33; nb. 5; (1990); p. 1452 - 1458 View in Reaxys

0.728 g

71 :A 100 mL pear-shaped flask was charged with 57(1.7 g, 7.3 mmol, 1 eq) and a stir bar. The flask was evacuated and backfilled with Ar (x3). Anhydrous THF (15 mL) was added, and the reaction was cooled to 0 °C with stirring. LAH (2.0 M in THF, 11 mL, 22 mmol, 3 eq) was added dropwise. The cooling bath was removed after the addition was completed. After 4 h at room temperature the reaction was cooled to 0 °C and cautiously quenched with Na2 SO4 (aq, saturated). The resulting mixture was filtered through Celite, rinsing with EtOAc. The layers were separated. The organic layer was washed with water (x2), brine (xl), and dried over Na2504. The solids were filtered off, and the volatiles were removed via rotary evaporation. The residue was DCM and dilute HC1 (pH 2), and the layers were separated. The aqueous layer was washed with DCM (xl). The aqueous layer was adjusted to pH 9 with NH4OH (aq, saturated) and extracted with EtOAc (x2). The combined EtOAc fractions were washed with brine (xl), and dried over Na2 SO4. The solids were filtered off, and the volatiles were removed via rotary evaporation yielding 0.728 g (3.55 mmol) of 58 as a colorless oil.

With lithium aluminium tetrahydride in tetrahydrofuran, Time= 4h, T= 0 - 20 °C , Inert atmosphere Patent; JORTAN PHARMACEUTICALS INC.; ANKALA, Sudha V.; LILLY, John C.; PEDDABUDDI, Gopal; (180 pag.); WO2017/66742; (2017); (A1) English View in Reaxys

O

HO

O

H 2N

Rx-ID: 21903668 View in Reaxys 2/6 Yield 63 %

Conditions & References Stage 1: With sodium azide, trifluoroacetic acid in dichloromethane, Time= 0.25h, T= -30 - 20 °C , Inert atmosphere Stage 2: With lithium aluminium tetrahydride in diethyl ether, Time= 3h, T= 20 °C Xu, Fan; Qian, Xiang-Yang; Li, Yan-Jie; Xu, Hai-Chao; Organic Letters; vol. 19; nb. 23; (2017); p. 6332 - 6335 View in Reaxys Reaction Steps: 2

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2018-07-31 10:57:05

1-(3-Methoxyphenyl)cyclohexan-1-amine (3-MeO-PCA) [C13H19NO]

1: NaN3, CF3COOH / CHCl3 / Ambient temperature 2: LiAlH4 / diethyl ether / 3 h With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in diethyl ether, chloroform Thurkauf, Andrew; Costa, Brian de; Yamaguchi, Shun-ichi; Mattson, Mariena V.; Jacobson, Arthur E.; et al.; Journal of Medicinal Chemistry; vol. 33; nb. 5; (1990); p. 1452 - 1458 View in Reaxys Reaction Steps: 2 1: sodium azide; trifluoroacetic acid / dichloromethane / 0 °C / Inert atmosphere 2: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, dichloromethane Patent; JORTAN PHARMACEUTICALS INC.; ANKALA, Sudha V.; LILLY, John C.; PEDDABUDDI, Gopal; (180 pag.); WO2017/66742; (2017); (A1) English View in Reaxys Br Mg

O

O

H 2N

Rx-ID: 21906338 View in Reaxys 3/6 Yield

Conditions & References Reaction Steps: 3 1: tetrahydrofuran / 0.33 h 2: NaN3, CF3COOH / CHCl3 / Ambient temperature 3: LiAlH4 / diethyl ether / 3 h With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, diethyl ether, chloroform Thurkauf, Andrew; Costa, Brian de; Yamaguchi, Shun-ichi; Mattson, Mariena V.; Jacobson, Arthur E.; et al.; Journal of Medicinal Chemistry; vol. 33; nb. 5; (1990); p. 1452 - 1458 View in Reaxys Reaction Steps: 3 1: tetrahydrofuran; toluene / 5.5 h / 0 °C / Inert atmosphere 2: sodium azide; trifluoroacetic acid / dichloromethane / 0 °C / Inert atmosphere 3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, dichloromethane, toluene Patent; JORTAN PHARMACEUTICALS INC.; ANKALA, Sudha V.; LILLY, John C.; PEDDABUDDI, Gopal; (180 pag.); WO2017/66742; (2017); (A1) English View in Reaxys O

O

H 2N

Rx-ID: 21931962 View in Reaxys 4/6 Yield

Conditions & References Reaction Steps: 3 1: tetrahydrofuran / 0.33 h 2: NaN3, CF3COOH / CHCl3 / Ambient temperature 3: LiAlH4 / diethyl ether / 3 h With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, diethyl ether, chloroform Thurkauf, Andrew; Costa, Brian de; Yamaguchi, Shun-ichi; Mattson, Mariena V.; Jacobson, Arthur E.; et al.; Journal of Medicinal Chemistry; vol. 33; nb. 5; (1990); p. 1452 - 1458 View in Reaxys

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2018-07-31 10:57:05

1-(3-Methoxyphenyl)cyclohexan-1-amine (3-MeO-PCA) [C13H19NO]

Reaction Steps: 3 1: tetrahydrofuran; toluene / 5.5 h / 0 °C / Inert atmosphere 2: sodium azide; trifluoroacetic acid / dichloromethane / 0 °C / Inert atmosphere 3: lithium aluminium tetrahydride / tetrahydrofuran / 4 h / 0 - 20 °C / Inert atmosphere With lithium aluminium tetrahydride, sodium azide, trifluoroacetic acid in tetrahydrofuran, dichloromethane, toluene Patent; JORTAN PHARMACEUTICALS INC.; ANKALA, Sudha V.; LILLY, John C.; PEDDABUDDI, Gopal; (180 pag.); WO2017/66742; (2017); (A1) English View in Reaxys Reaction Steps: 2 1.1: magnesium; iodine / tetrahydrofuran / 2 h / Reflux 1.2: 0 - 20 °C 2.1: sodium azide; trifluoroacetic acid / dichloromethane / 0.25 h / -30 - 20 °C / Inert atmosphere 2.2: 3 h / 20 °C With sodium azide, iodine, magnesium, trifluoroacetic acid in tetrahydrofuran, dichloromethane Xu, Fan; Qian, Xiang-Yang; Li, Yan-Jie; Xu, Hai-Chao; Organic Letters; vol. 19; nb. 23; (2017); p. 6332 - 6335 View in Reaxys

O

Br

H 2N

O

Rx-ID: 46912193 View in Reaxys 5/6 Yield

Conditions & References Reaction Steps: 2 1.1: magnesium; iodine / tetrahydrofuran / 2 h / Reflux 1.2: 0 - 20 °C 2.1: sodium azide; trifluoroacetic acid / dichloromethane / 0.25 h / -30 - 20 °C / Inert atmosphere 2.2: 3 h / 20 °C With sodium azide, iodine, magnesium, trifluoroacetic acid in tetrahydrofuran, dichloromethane Xu, Fan; Qian, Xiang-Yang; Li, Yan-Jie; Xu, Hai-Chao; Organic Letters; vol. 19; nb. 23; (2017); p. 6332 - 6335 View in Reaxys

O S

NH

O

H 2N

O

Rx-ID: 23587336 View in Reaxys 6/6 Yield 92 %

Conditions & References 57; 68 :To a 50 mL round-bottom flask was added the tert-butyl sulfinimine (1. 16 g, 3. 75 mmol), MeOH (20 mL) and HCI/ dioxane (5 mL) and allowed to stir at room temperature for 30 min. Disappearance of starting material was monitored by HPLC. The reaction was concentrated yielding a solid which was dried, rinsed with Et20 (2x), and dried again in vacuo. MS (ESI) 189.0.

With hydrogenchloride in 1,4-dioxane, methanol, Time= 0.5h, T= 20 °C Patent; ELAN PHARMACEUTICALS, INC.; WO2005/87215; (2005); (A1) English View in Reaxys

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