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

HRID 2045474Notes

Reaction equation

HRID 2045474 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([Cl:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[CH:16]=1)[C:11]([CH3:23])([CH3:22])[CH2:10]2)=[O:4].[CH:25]([C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)([CH3:27])[CH3:26].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([Cl:24])[CH:8]=[C:9]2[C:14]=1[NH:13][CH:12]([C:15]1[CH:16]=[C:17]([C:31]3[CH:32]=[CH:33][C:28]([CH:25]([CH3:27])[CH3:26])=[CH:29][CH:30]=3)[CH:18]=[CH:19][CH:20]=1)[C:11]([CH3:23])([CH3:22])[CH2:10]2)=[O:4]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27734804-Isopropylphenylboronic acidHCID 674420582-(3-Bromo-phenyl)-6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester

Product 1

HCID 674426006-Chloro-2-(4'-isopropyl-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl esterYield 53.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 2-(3-bromo-phenyl)-6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (680 mg, 1.67 mmol), 4-isopropylphenylboronic acid (320 mg, 2.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (193 mg, 0.17 mmol) in dioxane (5.0 mL) was added 2 M sodium carbonate solution in water (1.7 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 6-chloro-2-(4′-isopropyl-biphenyl-3-yl)-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-8-carboxylic acid methyl ester (400 mg, 53.4%) as a white solid: LC/MS m/e calcd for C28H30ClNO2 (M+H)+: 449.01, observed: 448.1.

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-be2bdab017fc41718e86b74e1596909a
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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