Ethyl Acetate → 2-(4'-Tert-butyl-5-fluoro-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester

HRID 1800979

Reaction equation

HRID 1800979 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]([C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[C:18](Br)[CH:17]=1)[C:10]([CH3:25])([CH3:24])[CH2:9]2)=[O:5])[CH3:2].[C:26]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)([CH3:29])([CH3:28])[CH3:27].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]([C:16]1[CH:17]=[C:18]([C:33]3[CH:34]=[CH:35][C:30]([C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:31][CH:32]=3)[CH:19]=[C:20]([F:22])[CH:21]=1)[C:10]([CH3:25])([CH3:24])[CH2:9]2)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27343204-tert-Butylphenylboronic acidHCID 674437712-(3-Bromo-5-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester

Product 1

HCID 674437852-(4'-Tert-butyl-5-fluoro-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl esterYield 37%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-(3-bromo-5-fluoro-phenyl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.41 g, 1.0 mmol), 4-tert-butylbenzeneboronic acid (0.36 g, 2.0 mmol), bis(triphenylphosphine)palladium (II) chloride (70.2 mg, 0.1 mmol) and 2 M sodium carbonate (1.5 mL, 3.0 mmol) in dioxane (5 mL) was heated for 3 hours at 120° C. After cooling to room temperature, the mixture was treated with ethyl acetate (50 mL) and washed with water (20 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. Purification on flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company) (10% ethyl acetate/hexanes) to afford 2-(4′-tert-butyl-5-fluoro-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (0.17 g, 37%) as a white solid: LC/MS m/e calcd for C30H34FNO2 (M+H)+: 460.6, observed: 460.3.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (20 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification on 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-1ab0df7cebe345fc8ba071dfc6da957d
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Linked notes

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