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

HRID 59079Notes

Reaction equation

HRID 59079 reaction equation
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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 241BenzeneSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-90efe18f134b4477812aa66321f48094
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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