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

HRID 414934

反応式

HRID 414934 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:17])[C:14]([OH:16])=[O:15])[CH:7]=[CH:6]2.[OH:18][CH2:19][C:20]([N+:25]([O-:27])=[O:26])([CH2:23]O)[CH2:21][OH:22].Cl.CN(C)CCCN=C=NCC.N(C(C)C)(C(C)C)CC>CN(C1C=CN=CC=1)C.CC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:17])[C:14]([O:16][CH2:23][C:20]([CH2:21][OH:22])([N+:25]([O-:27])=[O:26])[CH2:19][OH:18])=[O:15])[CH:7]=[CH:6]2

参加物

7

反応物 4

HCID 31337Tris(hydroxymethyl)nitromethaneHCID 81531DiisopropylethylamineHCID 156391NaproxenHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

生成物 1

HCID 210759623-Hydroxy-2-(hydroxymethyl)-2-nitropropyl (2S)-2-(6-methoxy(2-naphthyl))propanoate収率 39%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 180Acetone溶媒

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.

後処理

  1. customThe reaction mixture was evaporated to dryness
  2. customthe residue was partitioned between 3N HCl (100 mL) and CH2Cl2 (200 mL×2)
  3. washThe combined organic layer was back washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customdried under vacuum
  8. customThe product was separated by silica gel column chromatography
  9. washeluting with ethyl acetate/hexane (gradient from 1:2 to 1:1, Rf=0.1 in 1:2)

出典と根拠

ORDレコード
ord-cafb183cfe114494a12a49cc726c2c66
出典データセット
uspto-grants-2012_01
特許番号
US08088762B2

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