Ethyl trifluoroacetate → 1-(5-Bromopyridin-2-yl)-2,2,2-trifluoroethan-1-one

HRID 1487492Notes

Reaction equation

HRID 1487492 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.C([Li])CCC.C([O:16][C:17](=O)[C:18]([F:21])([F:20])[F:19])C>O1CCCC1.C1(C)C=CC=CC=1.[Cl-].[NH4+]>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:17](=[O:16])[C:18]([F:21])([F:20])[F:19])=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 9794Ethyl trifluoroacetateHCID 693532,5-DibromopyridineHCID 178418339Butyllithium

Product 1

HCID 672952111-(5-Bromopyridin-2-yl)-2,2,2-trifluoroethan-1-oneYield 68.8%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a stirred solution of 2, 5-Dibromo-pyridine (4 g, 6.87 mmol) in dry tetrahydrofuran (30 mL) and dry toluene (40 mL) is added drop wise n-Butyl lithium (1.62 g, 25.31 mmol) at −78° C. After stirring for 15-20 minutes, added trifluoro-acetic acid ethyl ester (3.56 g, 25.31 mmol) at −78° C. then stirred at −78° C. for another 30 minutes. The reaction mixture is diluted with saturated ammonium chloride solution and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, solvent is evaporated in vacuo and purified by column chromatography eluting in 20% ethyl acetate in hexane to afford the title compound (1.2 g). 1HNMR (400 MHz, DMSO-d6) δ: 7.72 (d, J=8.32 Hz, 1H), 7.85-7.88 (dd, J1=8.32 Hz, J2=2.44 Hz 1H), 8.52 (d, J=2.36 Hz, 1H). LC-MS (m/z): [M+H]=255.8.

Workup

  1. stirringthen stirred at −78° C. for another 30 minutes
  2. extractionextracted with ethyl acetate
  3. dry with materialOrganic layer is dried over sodium sulphate, solvent
  4. customis evaporated in vacuo
  5. custompurified by column chromatography
  6. washeluting in 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-eaab0dfc8a6442009e4901112f45af7c
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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