Potassium Carbonate → 4'-((R)-1-tert-Butoxycarbonylamino-ethyl)-3-chloro-3'-fluoro-biphenyl-2-carboxylic acid methyl ester

HRID 1404543Notes

Reaction equation

HRID 1404543 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[CH:12][C:11]=1[F:25])[CH3:9])([CH3:4])([CH3:3])[CH3:2].Br[C:28]1[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:29]=1[C:30]([O:32][CH3:33])=[O:31].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:33][O:32][C:30]([C:29]1[C:28]([C:13]2[CH:14]=[CH:15][C:10]([C@H:8]([NH:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:26])[CH3:9])=[C:11]([F:25])[CH:12]=2)=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:38])=[O:31]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 2759827Methyl 2-bromo-6-chlorobenzoateHCID 16102905{(R)-1-[2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethyl}-carbamic acid tert-butyl ester2×

Product 1

HCID 161028894'-((R)-1-tert-Butoxycarbonylamino-ethyl)-3-chloro-3'-fluoro-biphenyl-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of {(R)-1-[2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-ethyl}-carbamic acid tert-butyl ester (600 mg, 1.64 mmol, intermediate 13), methyl 2-bromo-6-chlorobenzoate (430 mg, 1.72 mmol) [CAS 685892-23-3; commercially available], tri-o-tolyl-phosphane (100 mg, 329 μmol), potassium carbonate (568 mg, 4.11 mmol) and palladium(II) acetate (18.4 mg, 82.1 μmol) in THF (20.0 ml) and water (1.18 ml) was stirred at room temperature over night. The reaction mixture was diluted with water and extracted three times with EtOAc. The combined extracts were washed with water and brine, dried with Na2SO4 and concentrated in vacuo. The remaining residue was purified by chromatography (silica gel; DCM/EtOAc 100:0-90:10) and the title compound was obtained as colorless oil (385 mg, 58%). MS: 466.1 [M−H+OAc]−.

Workup

  1. extractionextracted three times with EtOAc
  2. washThe combined extracts were washed with water and brine
  3. dry with materialdried with Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe remaining residue was purified by chromatography (silica gel; DCM/EtOAc 100:0-90:10)

Sources & evidence

ORD record
ord-25c274ec78ec4e9d9b610ddfaead1434
Source dataset
uspto-grants-2014_12
Patent number
US08912221B2

Reaction notes

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