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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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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1404543
[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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Komponenten

8

Edukt 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×

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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]−.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-25c274ec78ec4e9d9b610ddfaead1434
Quelldatensatz
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08912221B2

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