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

HRID 1910875Notes

Reaction equation

HRID 1910875 reaction equation
[NH3:1].Cl[C:3]1[N:8]=[C:7]([Cl:9])[C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=1>CO>[Cl:9][C:7]1[C:6]([C:10]([F:13])([F:12])[F:11])=[CH:5][N:4]=[C:3]([NH2:1])[N:8]=1

Participants

4

Reactant 2

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

Product 1

HCID 219231104-Chloro-5-(trifluoromethyl)pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Ammonia in methanol (7N solution, 15 mL) is added dropwise to the stirred neat 2,4-dichloro-5-(trifluoromethyl)pyrimidine (H-1) (5.0 g, 23.04 mmol) under argon, 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 (0-20% ethyl acetate-hexanes) to afford the product, 4-chloro-5-(trifluoromethyl)pyrimidin-2-amine (H-2) as a white solid. The regional-isomer, 2-chloro-5-(trifluoromethyl)pyrimidin-4-amine (H-3) can also be isolated as a white solid.

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 (0-20% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-4541d6fb4e9c42c7b1994f6d0822d5f8
Source dataset
uspto-grants-2013_12
Patent number
US08604032B2

Reaction notes

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