Hydrochloric Acid → 2-(6-Bromoquinolin-2-yl)-1,1,1-trifluoropropan-2-ol

HRID 1693072Notes

Reaction equation

HRID 1693072 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12](=[O:14])[CH3:13])[CH:6]=[CH:5]2.[F:15][C:16]([Si](C)(C)C)([F:18])[F:17].Cl>[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([OH:14])([CH3:13])[C:16]([F:18])([F:17])[F:15])[CH:6]=[CH:5]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 552549(Trifluoromethyl)trimethylsilaneHCID 574581651-(6-Bromoquinolin-2-yl)ethanone

Product 1

HCID 574581662-(6-Bromoquinolin-2-yl)-1,1,1-trifluoropropan-2-olYield 105.1%

Reagents, catalysts & solvents 2

HCID 2724141Tetrabutylammonium FluorideCatalystHCID 6228DimethylformamideSolvent

Procedure

A DMF (5 ml) solution of 1-(6-bromoquinolin-2-yl)ethanone (129 mg, 0.52 mmol), (trifluoromethyl)trimethylsilane (220 mg, 1.55 mmol) and tetrabutylammonium fluoride (13.5 mg, 0.052 mmol) was stirred at 100° C. for 2 hours. Then the mixture was cooled to room temperature and 1N-hydrochloride aqueous solution (2 ml) was added. After 4 hours, the mixture was quenched with saturated sodium bicarbonate aqueous solution, and the product was extracted with ethyl acetate which was dried over sodium sulfate. Then, filtration, evaporation and purification through silica gel column chromatography, eluting with hexane/ethyl acetate (4:1), furnished the title compound (175 mg, quant.) as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.81 (3H, s), 6.51 (1H, s), 7.64 (1H, d, J=8.1 Hz), 7.66-7.89 (1H, m), 8.00-8.12 (2H, m), 8.21 (1H, d, J=8.8 Hz). MS (ESI): m/z 320, 322 (M+H)+.

Workup

  1. customthe mixture was quenched with saturated sodium bicarbonate aqueous solution
  2. extractionthe product was extracted with ethyl acetate which
  3. dry with materialwas dried over sodium sulfate
  4. filtrationThen, filtration, evaporation and purification through silica gel column chromatography
  5. washeluting with hexane/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-28786fdef50f42f7923fb0988b47e921
Source dataset
uspto-grants-2012_04
Patent number
US08158650B2

Reaction notes

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