propofol

Query 1. Query

Query

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Date

RX.PXRN=18638792

2 reactions in Reaxys

2018-07-07 16h:02m:21s (UTC)

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HO O

O

O

O

O

O

OH

Rx-ID: 28003469 View in Reaxys 1/2 Yield

Conditions & References 1 :To a solution of 2, 6-diisopropylphenol (4. 0g, 22.4 mmol) in 15 mL of Et3N was added succinic anhydride (2.8g, 28 mmol) and a catalytic amount of DMAP (10 mg) under N2 atmosphere. The reaction mixture was stirred at ambient temperature overnight. The solvent was removed under vacuum and the residue was dissolved in water (30 mL) and added to a cold solution of 1 N HCI (150 mL). The precipitate was filtered and dried. Recrystallization from ethanol-water (2: 1) mixture gave 2,6- diisopropylphenyl hemisuccinate as a white crystalline solid. Yield : 5. 8 gram (94percent). 'H-NMR (CDCI3) 8 ppm : 1.2 (d, 12H), 2.82-2. 84 (m, 2H), 2.85-3. 0 (m, 4H), 7.1- 7.21 (m, 3H).

With triethylamine, dmap, T= 20 °C Patent; AUSPEX PHARMACEUTICALS, INC.; WO2005/44201; (2005); (A2) English View in Reaxys 1 : EXAMPLE 1 EXAMPLE 1 20 g of 2,6-diisopropylphenol (propofol) was dissolved in 50 ml of triethylamine, added with 14 g of succinyl oxide and 0.02 g of DMAP (4-dimethylamino-pyridine).The mixture was reacted completely for 16 hours under stirring at room temperature, and the reaction solution was evaporated under reduced pressure to remove triethylamine The residue was added into 100 ml of water and adjusted to pH 1 with 6N HCl to produce a great amount of white precipitate.

The precipitate was separated and then dried under reduced pressure to give crude propofol succinate monoester intermediate, which was recrystallized with cyclohexane/ethyl acetate to obtain 23.5 g of acicular crystals. Yield: 75.4percent, mp: 103-104° C. With dmap, triethylamine, Time= 16h, T= 20 °C Patent; West China Hospital Sichuan University; Zhang, Wensheng; Yang, Jun; Liu, Jin; US2013/79405; (2013); (A1) English View in Reaxys 1 : Example 1 Example 1 20 g of 2, 6-diisopropylphenol (propofol) was dissolved in 50 ml of triethylamine, added with 14 g of succinyl oxide and 0.02 g of DMAP (4-dimethylamino- pyridine).The mixture was reacted completely for 16 hours under stirring at room temperature, and the reaction solution was evaporated under reduced pressure to remove triethylamine.

The residue was added into 100 ml of water and adjusted to pH 1 with 6N HCl to produce a great amount of white precipitate.

The precipitate was separated and then dried under reduced pressure to give crude propofol succinate monoester intermediate, which was recrystallized with cyclohexane/ethyl acetate to obtain 23.5 g of acicular crystals. Yield: 75.4percent, mp: 103-104°C. Stage 1: With dmap, triethylamine, Time= 16h, T= 20 °C Stage 2: With hydrogenchloride in water, pH= 1 Patent; West China Hospital Sichuan University; ZHANG, Wensheng; YANG, Jun; LIU, Jin; EP2586768; (2013); (A1) English View in Reaxys 1 :10015] 20 g of propofol (II) was dissolved in 50 ml of triethylamine, added with 14 g of succinyl oxide and 0.02 g of DMAP (4-dimethylamino-pyridine). The mixture was reacted completely for 16 hours under stirring at room temperature, and the reaction solution was evaporated to remove triethylamine. The residue was added into 100 ml of water and adjusted to pH 1 with 6N HC1 to produce a great amount of white precipitate. The precipitate was separated and then dried under reduced pressure to give crude propofol succinate monoester (IV), which was recrystallized with cyclohexane/ ethyl acetate to obtain 23.5 g of acicular crystals. Yield:75.4percent, mp: 103-104° C. With dmap, triethylamine, Time= 16h, T= 20 °C

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Patent; Yichang Humanwell Pharmaceutical Co., Ltd.; West China Hospital, Sichuan University; Zhang, Wensheng; Yang, Jun; Liu, Jin; US2013/85120; (2013); (A1) English View in Reaxys With triethylamine Yang, Jun; Yin, Wang; Liu, Jin; Wang, Yu; Zhou, Cheng; Kang, Yi; Zhang, Wen-Sheng; Bioorganic and Medicinal Chemistry Letters; vol. 23; nb. 6; (2013); p. 1813 - 1816 View in Reaxys HO O O HO

O OH

O O OH

Rx-ID: 35298084 View in Reaxys 2/2 Yield

Conditions & References 2 : EXAMPLE 2 EXAMPLE 2 20 g of propofol was dissolved in 100 ml of methylene dichloride, added with 13.3 g of succinic acid, 0.02 g of dimethylaminopyridine, and then 23.2 g of DCC. The mixture was reacted for 6 hours under stirring at room temperature, then the reaction solution was filtrated to remove white solid and the filtrate was washed once with 150 ml of 6N HCl. The organic layer was separated and evaporated under reduced pressure to remove the solvent to give crude propofol succinate monoester intermediate as pale yellow solid, which was recrystallized with cyclohexane/ethyl acetate to obtain 26.6 g of white acicular crystals. Yield: 85percent, mp: 102-103° C. With dmap, dicyclohexyl-carbodiimide in dichloromethane, Time= 6h, T= 20 °C Patent; West China Hospital Sichuan University; Zhang, Wensheng; Yang, Jun; Liu, Jin; US2013/79405; (2013); (A1) English View in Reaxys 2 : Example 2 Example 2 20 g of propofol was dissolved in 100 ml of methylene dichloride, added with 13.3 g of succinic acid, 0.02 g of dimethylaminopyridine, and then 23.2 g of DCC. The mixture was reacted for 6 hours under stirring at room temperature, then the reaction solution was filtrated to remove white solid and the filtrate was washed once with 150 ml of 6N HCl. The organic layer was separated and evaporated under reduced pressure to remove the solvent to give crude propofol succinate monoester intermediate as pale yellow solid, which was recrystallized with cyclohexane/ethyl acetate to obtain 26.6 g of white acicular crystals. Yield: 85percent, mp: 102-103°C. Stage 1: With dmap, dicyclohexyl-carbodiimide in dichloromethane, Time= 6h, T= 20 °C Stage 2: With hydrogenchloride in water Patent; West China Hospital Sichuan University; ZHANG, Wensheng; YANG, Jun; LIU, Jin; EP2586768; (2013); (A1) English View in Reaxys 2 :[0026] 20 g of propofol was dissolved in 100 ml of methylenedichioride, addedwith 13.3 gofsuccinic acid, 0.02 gof DMAP, and then 23.2 g of DCC. The mixture was reacted for 6 hours under stirring at room temperature, then the reaction solution was filtrated to remove white solid, and the filtrate was washed once with 150 ml of 6N hydrochloric acid. The organic layer was separated and evaporated under reduced pressure to remove the solvent to give crude propofol succinate monoester (IV) as pale yellow solid, which was recrystallized with cyclohexane/ethyl acetate to obtain 26.6 g of white acicularcrystals.Yield: 85percent, mp: 102-103° C.10027] The method of preparing propofol w-hydroxybutyrate phosphate ester and/or its disodium salt (I) from propofol succinate monoester intermediate (IV) was similar to that of Example 1.

With dmap, dicyclohexyl-carbodiimide in dichloromethane, Time= 6h, T= 20 °C

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Patent; Yichang Humanwell Pharmaceutical Co., Ltd.; West China Hospital, Sichuan University; Zhang, Wensheng; Yang, Jun; Liu, Jin; US2013/85120; (2013); (A1) English View in Reaxys

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