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

HRID 1404543
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HRID 1404543 반응식
[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]
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참가 물질

8

반응물 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 ester2회

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

실험 절차

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]−.

후처리

  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)

출처 및 근거

ORD 기록
ord-25c274ec78ec4e9d9b610ddfaead1434
출처 데이터셋
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08912221B2

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