Acetic Acid → (2-Chloro-6-(1-ethoxyvinyl)pyrimidin-4-yl)methanol

HRID 59077Notes

Reaction equation

HRID 59077 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8](OC)=[O:9])[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[CH2:13])[N:3]=1.CN(C=O)C.[BH4-].[Na+].C(O)(=O)C>CO.O>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][OH:9])[CH:5]=[C:4]([C:12]([O:14][CH2:15][CH3:16])=[CH2:13])[N:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 4311764Sodium borohydrideHCID 117821404Methyl 2-chloro-6-(1-ethoxyvinyl)pyrimidine-4-carboxylate

Product 1

HCID 117820924(2-Chloro-6-(1-ethoxyvinyl)pyrimidin-4-yl)methanolYield 58.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Methyl 2-chloro-6-(1-ethoxyvinyl)pyrimidine-4-carboxylate (3.5 g, 14.4 mmol) was dissolved in MeOH (35 mL), DMF (24.50 mL) and water (3.5 mL) by careful heating. The mixture was cooled on an ice-bath and sodium borohydride (1.47 g, 38.9 mmol) was added in small portions (about 50 mg every 5 min) keeping the temperature below 5° C. After 3.5 h acetic acid (3.96 mL, 69.23 mmol) was added. MeOH was evaporated and water was added. The mixture was extracted with diisopropyl ether (3×50 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The product was purified by column chromatography on silica eluting with a gradient of EtOAc in heptane to give the title compound as a solid 1.8 g (58%).

Workup

  1. temperatureThe mixture was cooled on an ice-bath
  2. customthe temperature below 5° C
  3. customMeOH was evaporated
  4. additionwater was added
  5. extractionThe mixture was extracted with diisopropyl ether (3×50 mL)
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was purified by column chromatography on silica eluting with a gradient of EtOAc in heptane

Sources & evidence

ORD record
ord-c71deed5fb4f4a7fa870ee03a7073abb
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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