Sodium chlorodifluoroacetate → 2-Chloro-5-(difluoromethoxy)pyrimidine

HRID 250039Notes

Reaction equation

HRID 250039 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.Cl[C:10]([F:15])([F:14])C([O-])=O.[Na+]>CN(C)C=O.O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH:10]([F:15])[F:14])=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 2734985Sodium chlorodifluoroacetateHCID 145957002-Chloro-5-pyrimidinol

Product 1

HCID 574765572-Chloro-5-(difluoromethoxy)pyrimidineYield 39.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-Chloropyrimidin-5-ol (1 g, 7.66 mmol) and sodium 2-chloro-2,2-difluoroacetate (3.50 g, 22.98 mmol) in N,N-dimethylformamide (20 mL) and water (0.2 mL) were heated to 90° C. for 24 hours and concentrated in vacuo. The residue was purified by column chromatography (5-30% ethyl acetate/hexanes) to afford 2-chloro-5-(difluoromethoxy)pyrimidine (549 mg, 3.04 mmol, 39.7% yield) as a pale yellow oil. MS (LC/MS) R.T.=1.32; [M+H]+=181.14.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by column chromatography (5-30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-82afab17e4ab4b2eb1113edb84f6bf6c
Source dataset
uspto-grants-2011_01
Patent number
US07863291B2

Reaction notes

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