Sodium Carbonate → 2-(4'-Tert-butyl-biphenyl-3-yl)-6-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

HRID 2045504Notes

Reaction equation

HRID 2045504 reaction equation
COC([C:5]1[C:6]2[CH2:7][C:8]([CH3:24])([CH3:23])[CH:9]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18](Br)[CH:17]=3)[NH:10][C:11]=2[CH:12]=[CH:13][C:14]=1[F:15])=O.[C:25]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1)([CH3:28])([CH3:27])[CH3:26].[C:38](=[O:41])([O-])[O-:39].[Na+].[Na+].O1CCOC[CH2:45]1>O.C(OCC)(=O)C.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>[CH3:45][O:39][C:38]([C:12]1[CH:13]=[C:14]([F:15])[CH:5]=[C:6]2[C:11]=1[NH:10][CH:9]([C:16]1[CH:17]=[C:18]([C:32]3[CH:33]=[CH:34][C:29]([C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:30][CH:31]=3)[CH:19]=[CH:20][CH:21]=1)[C:8]([CH3:23])([CH3:24])[CH2:7]2)=[O:41]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27343204-tert-Butylphenylboronic acidHCID 674410152-(3-Bromo-phenyl)-6-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-5-carboxylic acid methyl ester

Product 1

HCID 674434052-(4'-Tert-butyl-biphenyl-3-yl)-6-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl esterYield 80%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture solution of 2-(3-bromo-phenyl)-6-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-5-carboxylic acid methyl ester (1.0 g, 2.6 mmol), 4-tert-butylphenylboronic acid (590 mg, 3.3 mmol) and tetrakis(triphenylphosphine)palladium(0) (289 mg, 0.25 mmol) in dioxane (5.0 mL) was added 2 M sodium carbonate solution in water (2.5 mL). The resulting mixture was subjected to microwave irradiation for 2 h at 110° C. The mixture was diluted with ethyl acetate (200 mL), washed with saturated aqueous sodium bicarbonate solution (50 mL×2), brine, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (10% ethyl acetate/hexanes) afforded 2-(4′-tert-butyl-biphenyl-3-yl)-6-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (926 mg, 80%) as a white solid: LC/MS m/e calcd for C29H32FNO2 (M+H)+: 446.58, observed: 446.1.

Workup

  1. customirradiation for 2 h at 110° C
  2. washwashed with saturated aqueous sodium bicarbonate solution (50 mL×2), brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-bf6a10326b0f4765bd3c44214edd26de
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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