Sodium hydride → (R)-4-((R)-1-tert-butoxyethyl)-3-(6-(difluoromethyl)-2-(methylthio)pyrimidin-4-yl)oxazolidin-2-one

HRID 57352ノート

反応式

HRID 57352 の反応式
[C:1]([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[CH3:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:15]1[CH:20]=[C:19]([CH:21]([F:23])[F:22])[N:18]=[C:17]([S:24][CH3:25])[N:16]=1.[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:15]1[CH:20]=[C:19]([CH:21]([F:23])[F:22])[N:18]=[C:17]([S:24][CH3:25])[N:16]=1)[CH3:7])([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 569729804-Chloro-6-(difluoromethyl)-2-(methylthio)pyrimidineHCID 90414930(R)-4-((R)-1-(tert-butoxy)ethyl)oxazolidin-2-one

生成物 1

HCID 90416007(R)-4-((R)-1-tert-butoxyethyl)-3-(6-(difluoromethyl)-2-(methylthio)pyrimidin-4-yl)oxazolidin-2-one収率 85%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of (R)-4-((R)-1-tert-butoxyethyl)oxazolidin-2-one (0.100 g, 0.534 mmol) and 4-chloro-6-(difluoromethyl)-2-(methylthio)pyrimidine (0.124 g, 0.587 mmol, 1.10 equiv) in DMF (2.7 mL) was treated with NaH (60%, 0.026 g, 0.64 mmol, 1.20 equiv), then the resulting mixture (yellow) was stirred at room temperature for 30 min. The reaction mixture was diluted with EtOAc (20 mL), washed with saturated aqueous NaCl (2×20 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 0 to 40%) provided (R)-4-((R)-1-tert-butoxyethyl)-3-(6-(difluoromethyl)-2-(methylthio)pyrimidin-4-yl)oxazolidin-2-one (0.164 g, white solid) in 85% yield. 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 6.45 (t, J=54 Hz, 1H), 4.80-4.72 (m, 1H), 4.66 (dd, J=9.4, 3.0 Hz, 1H), 4.49-4.34 (m, 2H), 2.58 (s, 3H), 1.25 (s, 9H), 1.02 (d, J=6.5 Hz, 3H); MS m/z 362.3 (M+H)+; Rt-1.09 min.

後処理

  1. washwashed with saturated aqueous NaCl (2×20 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

出典と根拠

ORDレコード
ord-2262e015b3b04e9cbd0b414c83423cba
出典データセット
uspto-grants-2016_09
特許番号
US09434719B2

反応ノート

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