Реакция #502116

Уравнение реакции

(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

Выход 39.0%

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

Выход 39.0%

Растворители

acetone

Условия реакции

Обработка

1. 1
   ДругоеThe reaction mixture was evaporated to dryness
2. 2
   Другоеthe residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2)
3. 3
   ПромывкаThe combined organic layer was back washed with water and brine
4. 4
   Сушкаdried over Na2SO4
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   Другоеdried under vacuum
8. 8
   ДругоеThe product was separated by silica gel column chromatography
9. 9
   Промывкаeluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2)

Методика

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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