Reacción #502108

Ecuación de reacción

(2S)-2-(6-methoxy(2-naphthyl))propanoic acid

2,2′-thiodiethanol

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

ether hexane

→

title compound

Rendimiento 81.5%

2-(2-Hydroxyethylthio)ethyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Rendimiento 81.5%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction mixture was partitioned between CH2Cl2 and water
2. 2
   Lavadothe water layer was washed with more CH2Cl2
3. 3
   LavadoThe combined organic layer was washed with water, 0.1 N HCl, water, brine
4. 4
   Secadodried over magnesium sulfate
5. 5
   ConcentraciónThe solution was concentrated under vacuum
6. 6
   Otrothe residue was purified via column chromatography, 5% ethyl acetate/dichloromethane
7. 7
   Otrothe solvent evaporated

Procedimiento

To a solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 15.0 g, 65 mmol), 2,2′-thiodiethanol (40 g, 325 mmol) and N,N-dimethylaminopyridine (DMAP, 1.59 g, 13 mmol) in dichloromethane (400 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDAC, 14.98g, 78 mmol) as a solid, in portions. After stirring for 3 hours at room temperature, TLC analysis indicated the reaction was complete. The reaction mixture was partitioned between CH2Cl2 and water, and the water layer was washed with more CH2Cl2. The combined organic layer was washed with water, 0.1 N HCl, water, brine, and dried over magnesium sulfate. The solution was concentrated under vacuum, and the residue was purified via column chromatography, 5% ethyl acetate/dichloromethane. The appropriate fractions were combined, and the solvent evaporated. Trituration of the residue with ether/hexane gave the title compound as a white solid (17.72 g, 81% yield). Mp 58-61° C. 1H NMR (300 MHz, CDCl3) δ 7.70 (d, J=8.6 Hz, 2H), 7.67 (d, J=0.9 Hz, 1H), 7.40 (dd, J=1.7, 8.5 Hz, 1H), 7.14 (dd, J=2.5, 8.8 Hz, 1H), 7.11 (d, J=2.5 Hz, 1H), 4.24 (t, J=6.7 Hz, 2H), 3.86 (q, J=7.2 Hz, 1H), 3.60 (app q, J=6.0 Hz, 2H), 2.69 (t, J=6.6 Hz, 2H), 2.61 (t, J=5.9 Hz, 2H), 2.00 (t, J=6.2 Hz, 1H), 1.59 (d, J=7.2 Hz, 3H). Mass spectrum (API-TIS) m/z 352 (MNH4+); Anal. calcd. for C18H22O4S: C, 64.65; H, 6.63; S, 9.59; Found: C, 64.62; H, 6.59; S, 9.47.

Fuente