tert-Butyl acrylate → 3-(3-Fluoro-4-formyl-phenyl)-acrylic acid tert-butyl ester

HRID 556277Notes

Reaction equation

Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([F:10])[CH:3]=1.C([O-])(O)=O.[Na+].[C:16]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])(=[O:19])[CH:17]=[CH2:18]>CN(C=O)C.C(N(CC)CC)C.O.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:21]([O:20][C:16](=[O:19])[CH:17]=[CH:18][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([F:10])[CH:3]=1)([CH3:24])([CH3:23])[CH3:22]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 4-bromo-2-fluoro benzaldehyde (2 g, 9.9 mmol) in DMF (50 ml) and triethylamine (6 ml) was degassed flushing N2 for 30 min. PPh3 (130 mg, 0.459 mmol), Pd(OAc)2 (44.3 mg, 0.20 mmol), NaHCO3 (1.6 g, 18.6 mmol) and tert-butyl acrylate (1.27 g, 9.9 mmol) were added and the resulting mixture was heated to reflux for 4 h. Additional tert-butyl acrylate (633 mg) and Pd(OAc)2 (20 mg) were added and the mixture was stirred at 100° C. for 3 h then the solution was diluted with H2O and extracted with Et2O. The organic layer was dried over Na2SO4 and the solvent was evaporated under vacuo to give the crude product that was purified by silica gel chromatography (petroleum ether/EtOAc 95:5). The collected fractions gave 2 g of 3-(3-fluoro-4-formyl-phenyl)-acrylic acid tert-butyl ester.

Workup

customflushing N2 for 30 min
temperaturethe resulting mixture was heated
temperatureto reflux for 4 h
extractionextracted with Et2O
dry with materialThe organic layer was dried over Na2SO4
customthe solvent was evaporated under vacuo
customto give the crude product that
customwas purified by silica gel chromatography (petroleum ether/EtOAc 95:5)

Sources & evidence

ORD record: ord-54b6be6704d7432fbc1eaa66244dd29a
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08058273B2

Reaction notes

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