반응 #502116

반응 방정식

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

2-hydroxymethyl-2-nitro-1,3-propanediol

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

NEt(i-Pr)2

→

title compound

수율 39.0%

3-Hydroxy-2-(hydroxymethyl)-2-nitropropyl (2S)-2-(6-methoxy(2-naphthyl))propanoate

수율 39.0%

용매

acetone

반응 조건

후처리

1. 1
   기타The reaction mixture was evaporated to dryness
2. 2
   기타the residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2)
3. 3
   세척The combined organic layer was back washed with water and brine
4. 4
   건조dried over Na2SO4
5. 5
   여과filtered
6. 6
   농축concentrated
7. 7
   기타dried under vacuum
8. 8
   기타The product was separated by silica gel column chromatography
9. 9
   세척eluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2)

실험 절차

A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 4.27 g, 18.5 mmol), 2-hydroxymethyl-2-nitro-1,3-propanediol (2.89 g, 19.1 mmol), N,N-dimethylaminopyridine (DMAP, 0.88 g, 7.2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.86 g, 25.4 mmol) and NEt(i-Pr)2 (11 mL, 63.2 mmol) in acetone (100 mL) was stirred at ambient temperature overnight. The reaction mixture was evaporated to dryness and the residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2). The combined organic layer was back washed with water and brine, dried over Na2SO4, filtered, concentrated and dried under vacuum. The product was separated by silica gel column chromatography eluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2) to give the title compound as a white solid (2.48 g, 39% yield). Mp 124-126° C. 1H NMR (300 MHz, 10% CD3OD/CDCl3) δ 7.73-7.64 (m, 3H), 7.37-7.33 (m, 1H), 7.17-7.12 (m, 2H), 4.44 (d, J=2.6 Hz, 2H), 3.92 (s, 3H), 3.9-3.7 (m, 5H), 3.4 (br, 2H), 1.58 (d, J=7.2 Hz, 3H), 13C NMR (75 MHz, 10% CD3OD/CDCl3) δ 174.1, 157.4, 134.5, 133.5, 129.0, 128.6, 127.0, 125.7, 118.8, 105.4, 92.4, 61.2, 60.1, 55.0, 45.0, 17.7.

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