4,6-Dichloropyrimidine → 4-Chloro-6-(3,3-difluoropyrrolidin-1-yl)pyrimidine

HRID 1723712Notes

Reaction equation

HRID 1723712 reaction equation
[F:1][C:2]1([F:7])[CH2:6][CH2:5][NH:4][CH2:3]1.[Cl:8][C:9]1[CH:14]=[C:13](Cl)[N:12]=[CH:11][N:10]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[Cl:8][C:9]1[CH:14]=[C:13]([N:4]2[CH2:5][CH2:6][C:2]([F:7])([F:1])[CH2:3]2)[N:12]=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 709434,6-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 27828273,3-Difluoropyrrolidine

Product 1

HCID 866171144-Chloro-6-(3,3-difluoropyrrolidin-1-yl)pyrimidineYield 48.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 3,3-difluoropyrrolidine (215 mg, 1.5 mmol), 4,6-dichloro-pyrimidine (223 mg, 1.5 mmol) and DIPEA (194 mg, 1.5 mmol) in 1,4-dioxane (3.0 mL) was heated at 100° C. for 16 hours. The reaction was cooled to room temperature and then partitioned between EtOAc and water. The organic phase was separated and washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated. The residue was separated with flash chromatography (25+S Biotage, 20% EtOAc/pentane) to afford 160 mg (48.6%) of 4-chloro-6-(3,3-difluoropyrrolidin-1-yl)pyrimidine as a solid.

Workup

  1. custompartitioned between EtOAc and water
  2. customThe organic phase was separated
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was separated with flash chromatography (25+S Biotage, 20% EtOAc/pentane)

Sources & evidence

ORD record
ord-e766658140db4f4da6337d45d5445dbc
Source dataset
uspto-grants-2009_02
Patent number
US07485641B2

Reaction notes

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