Reacción #502132

Ecuación de reacción

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

Rendimiento 30.0%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otropartitioned between dichloromethane and water
2. 2
   Lavadothe water layer was washed with more dichloromethane
3. 3
   LavadoThe combined organic layer was washed with water and brine
4. 4
   Secadodried over magnesium sulfate
5. 5
   ConcentraciónThe solution was concentrated under vacuum
6. 6
   Otrothe residue was purified via column chromatography, 50% ethyl acetate/hexane
7. 7
   Otrothe solvent removed by rotary evaporation
8. 8
   Otroto give an oil, 2.647 g, which

Procedimiento

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+).

Fuente