反応 #502116

反応方程式

(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

収率 39.0%

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

収率 39.0%

溶媒

acetone

反応条件

後処理

1. 1
   その他The reaction mixture was evaporated to dryness
2. 2
   その他the residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2)
3. 3
   洗浄The combined organic layer was back washed with water and brine
4. 4
   乾燥dried over Na2SO4
5. 5
   ろ過filtered
6. 6
   濃縮concentrated
7. 7
   その他dried under vacuum
8. 8
   その他The product was separated by silica gel column chromatography
9. 9
   洗浄eluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2)

実験手順

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.

出典