Water → 1-(2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanone

HRID 1482971Notes

Reaction equation

HRID 1482971 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12](Cl)=[O:13])=[CH:4][N:3]=1.[NH4+].[Cl-].O.[CH2:18]1COCC1>>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12](=[O:13])[CH3:18])=[CH:4][N:3]=1

Participants

5

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 27367082-Chloro-4-(trifluoromethyl)pyrimidine-5-carbonyl chloride

Product 1

HCID 220974501-(2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanoneYield 30%

Conditions

Temperature
-78 °C

Procedure

At −78° C., to a solution of 2-chloro-4-(trifluoromethyl)pyrimidine-5-carbonyl chloride (2.45 g, 10 mmol) in dry THF (50 mL) was added MeMgCl THF solution (3.0 M, 4 mL, 12 mmol) slowly and the reaction mixture was allowed to stir at −78° C. for 45 min. Sat. aq. NH4Cl (2 mL) and water (4 mL) were added. The aqueous layer was extracted with EtOAc (2×10 mL), and the combined extracts were dried with Na2SO4 and concentrated under reduced pressure. The crude residue was purified by silica chromatography eluting with EtOAc/hexanes (1/9) to give to give 1-(2-chloro-4-(trifluoromethyl)pyrimidin-5-yl)ethanone (675 mg, 30% yield). LC-MS m/z 225 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 8.86 (s, 1H), 2.65 (s, 3H).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  2. dry with materialthe combined extracts were dried with Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe crude residue was purified by silica chromatography
  5. washeluting with EtOAc/hexanes (1/9)
  6. customto give

Sources & evidence

ORD record
ord-90267535d3b847a4bd725e3cb61700e3
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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