تفاعل #502116

ord-cafb183cfe114494a12a49cc726c2c66

معادلة التفاعل

COc1ccc2cc([C@H](C)C(=O)O)ccc2c1
(2S)-2-(6-methoxy(2-naphthyl))propanoic acid
O=[N+]([O-])C(CO)(CO)CO
2-hydroxymethyl-2-nitro-1,3-propanediol
CCN=C=NCCCN(C)C.Cl
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
CCN(C(C)C)C(C)C
NEt(i-Pr)2
COc1ccc2cc([C@H](C)C(=O)OCC(CO)(CO)[N+](=O)[O-])ccc2c1
title compound
المردود 39.0%
COc1ccc2cc([C@H](C)C(=O)OCC(CO)(CO)[N+](=O)[O-])ccc2c1
3-Hydroxy-2-(hydroxymethyl)-2-nitropropyl (2S)-2-(6-methoxy(2-naphthyl))propanoate
المردود 39.0%

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىThe reaction mixture was evaporated to dryness
  2. 2
    أخرىthe residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2)
  3. 3
    غسيلThe combined organic layer was back washed with water and brine
  4. 4
    تجفيفdried over Na2SO4
  5. 5
    ترشيحfiltered
  6. 6
    تركيزconcentrated
  7. 7
    أخرىdried under vacuum
  8. 8
    أخرىThe product was separated by silica gel column chromatography
  9. 9
    غسيلeluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2)

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08088762B2uspto-grants-2012_01