반응 #502108

반응 방정식

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

2,2′-thiodiethanol

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

ether hexane

→

title compound

수율 81.5%

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

수율 81.5%

용매

dichloromethane

반응 조건

후처리

1. 1
   기타The reaction mixture was partitioned between CH2Cl2 and water
2. 2
   세척the water layer was washed with more CH2Cl2
3. 3
   세척The combined organic layer was washed with water, 0.1 N HCl, water, brine
4. 4
   건조dried over magnesium sulfate
5. 5
   농축The solution was concentrated under vacuum
6. 6
   기타the residue was purified via column chromatography, 5% ethyl acetate/dichloromethane
7. 7
   기타the solvent evaporated

실험 절차

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.

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