Sodium hydride → HCID 86730137、化合物

HRID 1850108ノート

反応式

HRID 1850108 の反応式
[F:1][C:2]1[N:7]=[C:6](F)[CH:5]=[CH:4][N:3]=1.[CH:9]([C@H:12]1[CH2:16][O:15][C:14](=[O:17])[NH:13]1)([CH3:11])[CH3:10].[H-].[Na+]>CN(C=O)C.O>[F:1][C:2]1[N:7]=[C:6]([N:13]2[C@@H:12]([CH:9]([CH3:11])[CH3:10])[CH2:16][O:15][C:14]2=[O:17])[CH:5]=[CH:4][N:3]=1

参加物

6

反応物 3

HCID 24758Sodium hydrideHCID 1377162,4-DifluoropyrimidineHCID 7157133(4S)-4-(propan-2-yl)-1,3-oxazolidin-2-one

生成物 1

HCID 86730137HCID 86730137、化合物収率 33.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 2,4-difluoropyrimidine (3.5 mL, 41 mmol) and (S)-4-isopropyloxazolidin-2-one (5.3 g 41 mmol) in 30 mL DMF was cooled to 0° C. under N2 atmosphere. NaH (2.1 g of 60% suspension, 53 mmol) was slowly added. Bubbling exotherm observed. Internal temp was kept below 5° C. After 5 minutes, cold bath was removed. Reaction mixture (a sandy suspension) was allowed to warm to room temp and stir 18 h. The reaction mixture was diluted with water (100 mL) and extracted with (3×75 mL) EtOAc. Organic layer was washed with 50 mL each water, and brine. Dried over Na2SO4, and concentrated on silica gel in vacuo. Column chromatography (EtOAc/heptane 10 to 100% gradient) gave 3.1 g (S)-3-(2-fluoropyrimidin-4-yl)-4-isopropyloxazolidin-2-one (IV) as a crystalline white solid (33%). 1H NMR (400 MHz, CDCl3) δ 8.50 (dd, J=5.8, 2.2 Hz, 1H), 8.19 (dd, J=5.8, 3.8 Hz, 1H), 4.79 (dt, J=8.1, 3.5 Hz, 1H), 4.48-4.34 (m, 2H), 2.64 (heptd, J=7.0, 3.6 Hz, 1H), 1.01 (d, J=7.0 Hz, 3H), 0.90 (d, J=6.9 Hz, 3H). MS m/z 471.8 and 471.8 (M+H)+.

後処理

  1. customBubbling exotherm
  2. customwas kept below 5° C
  3. customcold bath was removed
  4. customReaction mixture (a sandy suspension)
  5. extractionextracted with (3×75 mL) EtOAc
  6. washOrganic layer was washed with 50 mL each water, and brine
  7. dry with materialDried over Na2SO4
  8. concentrationconcentrated on silica gel in vacuo

出典と根拠

ORDレコード
ord-695de0d84b834df996520af7df416920
出典データセット
uspto-grants-2015_02
特許番号
US08957068B2

反応ノート

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