Methanol → Methyl 2-(2,2,2-trifluoro-1,1-dimethylethyl)quinoline-6-carboxylate

HRID 1094660Notes

Reaction equation

HRID 1094660 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([CH3:18])([CH3:17])[C:13]([F:16])([F:15])[F:14])[CH:6]=[CH:5]2.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:55][OH:56].CN([CH:60]=[O:61])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:14][C:13]([F:16])([F:15])[C:12]([C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:55]([O:61][CH3:60])=[O:56])[CH:3]=2)[N:8]=1)([CH3:18])[CH3:17]

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 574581686-Bromo-2-(2,2,2-trifluoro-1,1-dimethylethyl)quinoline

Product 1

HCID 57458169Methyl 2-(2,2,2-trifluoro-1,1-dimethylethyl)quinoline-6-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A mixture of the 6-bromo-2-(2,2,2-trifluoro-1,1-dimethylethyl)quinoline (950 mg, 3.0 mmol), triethylamine (1.25 ml, 9.0 mmol), 1,3-bis(diphenylphosphino)propane (123 mg, 0.3 mmol), palladium acetate (67 mg, 0.3 mmol) and methanol (4.8 ml) in DMF (10 ml) was stirred at reflux under carbon monoxide (1 atm) for 16 hours. Then the reaction was quenched with saturated sodium bicarbonate aqueous solution and the product was extracted with ethyl acetate and dried over sodium sulfate. Then, filtration, evaporation, purification through silica gel column chromatography eluting with hexane/ethyl acetate (25:1) furnished the title compound (777 mg, 88% yield) as a white solid. 1H NMR (300 MHz, CDCl3) ppm 1.74 (6H, s), 4.00 (3H, s), 7.71 (1H, d, J=8.8 Hz), 8.14 (1H, d, J=8.8 Hz), 8.25 (1H, d, J=8.8 Hz), 8.28-8.32 (1H, m), 8.58-8.59 (1H, m). MS (ESI): m/z 298 (M+H)+.

Workup

  1. temperatureat reflux under carbon monoxide (1 atm) for 16 hours
  2. customThen the reaction was quenched with saturated sodium bicarbonate aqueous solution
  3. extractionthe product was extracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. filtrationThen, filtration, evaporation, purification through silica gel column chromatography
  6. washeluting with hexane/ethyl acetate (25:1)

Sources & evidence

ORD record
ord-815f4b67916d4ff08c44209382021465
Source dataset
uspto-grants-2012_03
Patent number
US08134004B2

Reaction notes

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