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

HRID 59079노트

반응식

HRID 59079 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 94433Tetrabutylammonium hydrogen sulfate촉매HCID 241Benzene용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-90efe18f134b4477812aa66321f48094
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09439904B2

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