Methyl Acrylate → tert-Butyl 1-(2-methoxy-2-oxoethyl)isoindoline-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

3-[2-(tert-Butoxycarbonylamino-methyl)-phenyl]-acrylic acid methyl ester: To a solution of 161.0 g (561.8 mmol) of material from Part A, 58.0 g (674.2 mmol) of methyl acrylate and 170.5 g (1685.4 mmol) of triethylamine in 800 mL of N,N-dimethylformamide was added 7.9 g (11.2 mmol) of dichlorobis(triphenylphosphine)palladium(II) and the mixture was heated at 80° C. for 32 hr. The mixture was cooled, diluted with 1000 mL of ethyl acetate and washed with 10% aqueous sodium bisulfate. The aqueous portion was extracted three times with ethyl acetate and the combined organics were dried (Na2SO4), filtered and concentrated in vacuo. The residue was dissolved in a small amount of dichloromethane and filtered through 7 in. of silica gel in a 2 L sintered glass funnel eluting with 25% ethyl acetate/hexanes. The eluant was concentrated in vacuo and recrystallized from ethyl acetate/hexanes to afford 116.9 g (71%) of the title compound.

Provenance & Evidence