Potassium Carbonate → HCID 86682939, compound

HRID 1497072Notes

Reaction equation

HRID 1497072 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([CH:17]([CH3:19])[CH3:18])=[N:7][C:8]2[C:13]([C:14]=1Br)=[CH:12][C:11]([Cl:16])=[CH:10][CH:9]=2)=[O:4].C([O-])([O-])=O.[K+].[K+].[F:26][C:27]([F:39])([F:38])[O:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:6]([CH:17]([CH3:19])[CH3:18])=[N:7][C:8]2[C:13]([C:14]=1[C:31]1[CH:32]=[CH:33][CH:34]=[C:29]([O:28][C:27]([F:26])([F:38])[F:39])[CH:30]=1)=[CH:12][C:11]([Cl:16])=[CH:10][CH:9]=2)=[O:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 86682940HCID 86682940, compound

Product 1

HCID 86682939HCID 86682939, compoundYield 43.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-bromo-6-chloro-2-isopropyl-quinoline-3-carboxylic acid methyl ester (150 mg, 0.44 mmol), K2CO3 (183 mg, 1.31 mmol) and 3-trifluoromethoxyphenylboronic acid (61 mg, 0.35 mmol) in dimethyl formamide (4 ml) in a sealed tube was purged with argon for 20 min followed by addition of Pd(PPh3)4 (51 mg, 0.04 mmol), again purged with argon for 10 min and the reaction mixture was heated at 90° C. for 5 h under stirring. After cooling, the reaction mixture was filtered through celite bed and washed with ethyl acetate. The organic phase was concentrated in vacuo and then partitioned between water and ethyl acetate. The organic phase was separated and washed with brine, dried over sodium sulfate and concentrated in vacuo to afford a crude residue. This crude residue was purified by flash column chromatography (100-200 mesh silica, eluting with 2% EtOAc in hexane) to afford pure 6-chloro-2-isopropyl-4-(3-trifluoromethoxy-phenyl)-quinoline-3-carboxylic acid methyl ester (65 mg, 35%) as pale yellow sticky liquid. LC-MS: 424 (M+H)+.

Workup

  1. customwas purged with argon for 20 min
  2. customagain purged with argon for 10 min
  3. temperatureAfter cooling
  4. filtrationthe reaction mixture was filtered through celite bed
  5. washwashed with ethyl acetate
  6. concentrationThe organic phase was concentrated in vacuo
  7. custompartitioned between water and ethyl acetate
  8. customThe organic phase was separated
  9. washwashed with brine
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated in vacuo
  12. customto afford a crude residue
  13. customThis crude residue was purified by flash column chromatography (100-200 mesh silica, eluting with 2% EtOAc in hexane)

Sources & evidence

ORD record
ord-b1a2b583f6f542c6af7bd0eeeba733db
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

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