Reaktion #502108

Reaktionsgleichung

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

2,2′-thiodiethanol

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

ether hexane

→

title compound

Ausbeute 81.5%

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

Ausbeute 81.5%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction mixture was partitioned between CH2Cl2 and water
2. 2
   Waschenthe water layer was washed with more CH2Cl2
3. 3
   WaschenThe combined organic layer was washed with water, 0.1 N HCl, water, brine
4. 4
   Trocknendried over magnesium sulfate
5. 5
   EinengenThe solution was concentrated under vacuum
6. 6
   Sonstigethe residue was purified via column chromatography, 5% ethyl acetate/dichloromethane
7. 7
   Sonstigethe solvent evaporated

Vorschrift

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.

Quelle