Sodium Hydroxide → 2-Chloro-4-(((3,3-difluorocyclobutyl)methoxy)methyl)-6-(1-ethoxyvinyl)pyrimidine

HRID 59079ノート

反応式

HRID 59079 の反応式
CS([O:5][CH2:6][C:7]1[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[CH2:14])[N:10]=[C:9]([Cl:18])[N:8]=1)(=O)=O.[F:19][C:20]1([F:26])[CH2:23][CH:22]([CH2:24]O)[CH2:21]1.[OH-].[Na+]>C1C=CC=CC=1.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:18][C:9]1[N:8]=[C:7]([CH2:6][O:5][CH2:24][CH:22]2[CH2:23][C:20]([F:26])([F:19])[CH2:21]2)[CH:12]=[C:11]([C:13]([O:15][CH2:16][CH3:17])=[CH2:14])[N:10]=1

参加物

6

反応物 3

HCID 14798Sodium HydroxideHCID 45480377(3,3-Difluorocyclobutyl)methanolHCID 117821115(2-Chloro-6-(1-ethoxyvinyl)pyrimidin-4-yl)methyl methanesulfonate

生成物 1

HCID 1178207002-Chloro-4-(((3,3-difluorocyclobutyl)methoxy)methyl)-6-(1-ethoxyvinyl)pyrimidine収率 20.2%

試薬・触媒・溶媒 2

HCID 94433Tetrabutylammonium hydrogen sulfate触媒HCID 241Benzene溶媒

実験手順

To a solution of (2-chloro-6-(1-ethoxyvinyl)pyrimidin-4-yl)methyl methanesulfonate (0.5 g, 1.71 mmol) in benzene (8 mL) were added (3,3-difluorocyclobutyl)methanol (0.313 g, 2.56 mmol), sodium hydroxide (aq, 5 M, 0.512 mL, 2.56 mmol) and tetrabutylammonium hydrogen sulfate (0.058 g, 0.17 mmol). The mixture was stirred vigorously at rt for 72 h. The mixture was extracted with diethylether. The organic phase was washed with 50% brine, dried over magnesium sulfate and the solvent was evaporated to give 484 mg crude product. 123 mg material from a different batch synthesized using the same method was added. The residue was purified by column chromatography on silica eluting with a gradient of EtOAc in heptane to give the title compound as a gum (0.110 g, 20%).

後処理

  1. extractionThe mixture was extracted with diethylether
  2. washThe organic phase was washed with 50% brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated
  5. customto give 484 mg crude product
  6. additionwas added
  7. customThe residue was purified by column chromatography on silica eluting with a gradient of EtOAc in heptane

出典と根拠

ORDレコード
ord-90efe18f134b4477812aa66321f48094
出典データセット
uspto-grants-2016_09
特許番号
US09439904B2

反応ノート

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