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

HRID 1527487Notes

Reaction equation

HRID 1527487 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

5

Reactant 4

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 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).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 7 h
  3. concentrationThe reaction mixture was concentrated in vacuo to half of the volume
  4. customquenched by addition of saturated aqueous NaHCO3
  5. extractionextracted with EtOAc
  6. dry with materialAfter drying (Na2SO4) the solvent
  7. customwas removed in vacuo
  8. customthe residue was purified by flash column chromatography on silica gel (eluent: hexane/EtOAc 9:1 to 4:1)

Sources & evidence

ORD record
ord-cfb27d4d86444e32856b9edc89b2532d
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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