Water → (3-Chloro-2-fluoro-5-vinyl-benzyl)-carbamic acid tert-butyl ester

Reaction equation

[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:14]=[C:13](Br)[CH:12]=[C:11]([Cl:16])[C:10]=1[F:17])([CH3:4])([CH3:3])[CH3:2].O.C([O-])([O-])=O.[K+].[K+].CO[CH2:28][CH2:29]OC>>[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([CH:28]=[CH2:29])[CH:12]=[C:11]([Cl:16])[C:10]=1[F:17])([CH3:4])([CH3:3])[CH3:2]

Participants

Reactant 4

HCID 962Water

HCID 80711,2-Dimethoxyethane

HCID 11430Potassium Carbonate

HCID 68283623Carbamic acid, N-[(5-bromo-3-chloro-2-fluorophenyl)methyl]-, 1,1-dimethylethyl ester

Product 1

HCID 68283690(3-Chloro-2-fluoro-5-vinyl-benzyl)-carbamic acid tert-butyl ester

Procedure

To a solution of (5-bromo-3-chloro-2-fluoro-benzyl)-carbamic acid tert-butyl ester (6 g, 17.7 mmol) in DME (100 mL) was added Pd(Ph3)4 (1.0 g, 0.9 mmol) under argon atmosphere and the mixture was stirred for 30 min at ambient temperature. After addition of vinyl boronic anhydride pyridine complex (4.3 g, 17.7 mmol), water (25 mL) and K2CO3 (2.45 g, 17.7 mmol) the reaction was heated under reflux for 7 h. The reaction mixture was concentrated in vacuo to half of the volume, quenched by addition of saturated aqueous NaHCO3 and extracted with EtOAc. After drying (Na2SO4) the solvent was removed in vacuo and the residue was purified by flash column chromatography on silica gel (eluent: hexane/EtOAc 9:1 to 4:1) to afford the title compound as a colorless oil. 1H-NMR (500 MHz, DMSO): δ (ppm) 7.62 (d, 1H), 7.45 (m, 1H, —NH), 7.35 (d, 1H), 6.68 (dd, 1H), 5.82 (d, 1H), 5.32 (d, 1H), 4.18 (d, 2H), 1.39 (s, 9H).