Methyl Acrylate → (S)-2-[4-((E)-2-methoxycarbonyl-vinyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of (S)-2-(4-bromo-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (44.0 g, 128 mmol) in 1,4-dioxane (500 mL) in a sealed pressure vessel was sequentially added N-methyldicyclohexylamine (32.9 mL, 154 mmol), (t-Bu)3HBF4 (1.19 g, 4.10 mmol), methyl acrylate (34.8 mL, 385 mmol) and Pd2(dba)3 (1.19 g, 1.29 mmol). The reaction mixture was heated to 150° C. in a sealed pressure vessel for 4.5 h then cooled in ice bath and placed in refrigerator for 16 h. The reaction mixture was filtered through a Celite pad, the filter cake was washed with 250 mL ethyl acetate, and the combined organics were concentrated in vacuo to a yellow oil. The oil was taken up in 20% ethyl acetate in heptane, sonicated and filtered, and the filtrate was concentrated again in vacuo. The residue was dissolved in ethyl acetate and the organic solution was washed sequentially with 10% citric acid, sodium bicarbonate solution and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel column chromatography (ethyl acetate/heptane) or recrystallized from 20% ethyl acetate in heptane. Total recovery is 42.1 g (99% yield).

Provenance & Evidence