Methyl trifluoromethyl ketone → 2-(2-Chloropyrimidin-5-yl)-1,1,1-trifluoropropan-2-ol

HRID 1972344Notes

Reaction equation

HRID 1972344 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[Li]CCCC.[F:14][C:15]([F:20])([F:19])[C:16](=[O:18])[CH3:17]>CCOCC>[Cl:8][C:5]1[N:4]=[CH:3][C:2]([C:16]([OH:18])([CH3:17])[C:15]([F:20])([F:19])[F:14])=[CH:7][N:6]=1

Participants

5

Reactant 3

HCID 9871Methyl trifluoromethyl ketoneHCID 6066655-Bromo-2-chloropyrimidineHCID 178418339Butyllithium

Product 1

HCID 866703602-(2-Chloropyrimidin-5-yl)-1,1,1-trifluoropropan-2-olYield 17%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

A 500-mL round-bottomed flask was charged with 5-bromo-2-chloropyrimidine (8.53 g, 44.1 mmol, Combi-Blocks, San Diego, Calif.) and 100 mL of ether. After cooling to −78° C., n-BuLi (2.5 M in hexanes, 27.6 mL, 44.1 mmol) was added. This mixture was stirred at −78° C. for 10 min, then 1,1,1,tri-fluoro-2-propanone (14.82 g, 132 mmol, Sigma-Aldrich, St. Louis, Mo.) was added. After stirring for an additional 10 min at −78° C., the reaction was quenched with saturated aqueous NH4Cl. The solution was extracted with EtOAc, dried (MgSO4), filtered, and concentrated. Purification via column chromatography on silica gel (0 to 85% EtOAc in hexanes) gave 2-(2-chloro-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (1.70 g) as a white solid.

Workup

  1. stirringAfter stirring for an additional 10 min at −78° C.
  2. customthe reaction was quenched with saturated aqueous NH4Cl
  3. extractionThe solution was extracted with EtOAc
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification via column chromatography on silica gel (0 to 85% EtOAc in hexanes)

Sources & evidence

ORD record
ord-fb46de17a895425fbda74e9c87baa68a
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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