تفاعل #502108

معادلة التفاعل

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

2,2′-thiodiethanol

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

ether hexane

→

title compound

المردود 81.5%

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

المردود 81.5%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction mixture was partitioned between CH2Cl2 and water
2. 2
   غسيلthe water layer was washed with more CH2Cl2
3. 3
   غسيلThe combined organic layer was washed with water, 0.1 N HCl, water, brine
4. 4
   تجفيفdried over magnesium sulfate
5. 5
   تركيزThe solution was concentrated under vacuum
6. 6
   أخرىthe residue was purified via column chromatography, 5% ethyl acetate/dichloromethane
7. 7
   أخرىthe solvent evaporated

الإجراء التجريبي

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.

المصدر