Réaction #502132

Équation de réaction

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

Rendement 30.0%

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   Autrepartitioned between dichloromethane and water
2. 2
   Lavagethe water layer was washed with more dichloromethane
3. 3
   LavageThe combined organic layer was washed with water and brine
4. 4
   Séchagedried over magnesium sulfate
5. 5
   ConcentrationThe solution was concentrated under vacuum
6. 6
   Autrethe residue was purified via column chromatography, 50% ethyl acetate/hexane
7. 7
   Autrethe solvent removed by rotary evaporation
8. 8
   Autreto give an oil, 2.647 g, which

Mode opératoire

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+).

Source