Réaction #502116

Équation de réaction

(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

Rendement 39.0%

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

Rendement 39.0%

Solvants

acetone

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture was evaporated to dryness
2. 2
   Autrethe residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2)
3. 3
   LavageThe combined organic layer was back washed with water and brine
4. 4
   Séchagedried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   Autredried under vacuum
8. 8
   AutreThe product was separated by silica gel column chromatography
9. 9
   Lavageeluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2)

Mode opératoire

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.

Source