Ammonia → 4-Chloro-5-(trifluoromethyl)pyrimidin-2-amine

HRID 1626910Notes

Reaction equation

HRID 1626910 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH3:13]>CO>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH2:13])[N:7]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidine

Product 1

HCID 219231104-Chloro-5-(trifluoromethyl)pyrimidin-2-amineYield 22.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To stirred neat 2,4-dichloro-5-(trifluoromethyl)pyrimidine (F-1) (5.0 g, 23.04 mmol) under argon, ammonia in methanol (7N solution, 15 mL) is added dropwise and the resulting mixture is stirred at RT for 2 h. The reaction mixture is quenched with water and then extracted with ethyl acetate (200 mL×2). The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo and the residue is purified by flash chromatography on silica gel eluting with 0-20% ethyl acetate/hexanes to afford the product, 4-chloro-5-(trifluoromethyl)pyrimidin-2-amine (F-2) (1.03 g, 22.6% yield). The other regio-isomer, 2-chloro-5-(trifluoromethyl)pyrimidin-4-amine (F-3), can also be isolated.

Workup

  1. customThe reaction mixture is quenched with water
  2. extractionextracted with ethyl acetate (200 mL×2)
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate is concentrated in vacuo
  7. customthe residue is purified by flash chromatography on silica gel eluting with 0-20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-3ab4d5a02fde4be69e6370bf02fc3bbc
Source dataset
uspto-grants-2014_07
Patent number
US08785470B2

Reaction notes

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