Реакция #502132

Уравнение реакции

naproxen

4-mercapto-l-butanol

1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride

4-mercapto-l-butanol

→

(2S)-1-(4-Hydroxybutylthio)-2-(6-methoxy(2-naphthyl))propan-1-one

Выход 30.0%

Растворители

dichloromethane

Условия реакции

Обработка

1. 1
   Другоеpartitioned between dichloromethane and water
2. 2
   Промывкаthe water layer was washed with more dichloromethane
3. 3
   ПромывкаThe combined organic layer was washed with water and brine
4. 4
   Сушкаdried over magnesium sulfate
5. 5
   КонцентрированиеThe solution was concentrated under vacuum
6. 6
   Другоеthe residue was purified via column chromatography, 50% ethyl acetate/hexane
7. 7
   Другоеthe solvent removed by rotary evaporation
8. 8
   Другоеto give an oil, 2.647 g, which

Методика

To a solution of naproxen (5.03 g, 21.9 mmol), 4-mercapto-l-butanol (2.32 g, 21.9 mmol) and N,N-dimethylaminopyridine (DMAP) (0.534 g, 4.37 mmol) in dichloromethane (200 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDAC) (5.03 g, 26.2 mmol) as a solid, in portions. The reaction mixture was stirred for 3 hours at room temperature, then partitioned between dichloromethane and water, and the water layer was washed with more dichloromethane. The combined organic layer was washed with water and brine, then dried over magnesium sulfate. The solution was concentrated under vacuum, and the residue was purified via column chromatography, 50% ethyl acetate/hexane. The appropriate fractions were combined, and the solvent removed by rotary evaporation to give an oil, 2.647 g, which contained 19% 4-mercapto-l-butanol by weight (product weight 2.07 g, 6.5 mmol, 30% yield): 1H NMR (300 MHz, CDCl3) δ 7.73 (d, J=2.7 Hz, 1H), 7.71 (d, J=2.3 Hz, 1H), 7.69 (d, J=1.0 Hz, 1H), 7.40 (dd, J=1.8, 8.5 Hz, 1H), 7.15 (dd, J=2.5, 8.8 Hz, 1H), 7.12 (d, J=2.3 Hz, 1H), 4.02 (q, J=7.1 Hz, 1H), 3.92 (s, 3H), 3.61-3.64 (m, 2H), 2.87 (m, 2H), 1.61 (d, J=7.1 Hz, 3H), 1.59 (m, 2H), 1.41 (m, 2H); mass spectrum (API-TIS) m/z 319 (M+H+), 336 (M+18+).

Источник