Trifluoroacetic acid → Ethyl 1-benzylpyrrolidine-3-carboxylate

Participants

Reaction Steps

To a stirred solution of ethyl acrylate (141 g, 1.41 mole) and N-benzyl-N-(methoxymethyl)-N-[(trimethylsilyl)methyl]amine (Compound D17 of EP 0363085, 435 g, containing approximately 75% of D17, 1.4 moles) in dichloromethane (2.5L) at -5° C. was added trifluoroacetic acid (16.1 g, 0.14 mole) in dichloromethane (100 ml) ensuring that the temperature did not rise above 0° C. This mixture was then transferred by cannula to stirred, refluxing dichloromethane (50 ml) over 40 minutes at such a rate as to maintain gentle reflux. The reaction mixture was then refluxed for a further 1h before cooling to room temperature. It was then washed with saturated aqueous potassium carbonate, dried (Na2SO4), and concentrated in vacuo to a gum which was distilled to afford the title compound (D1) as a clear oil (286 g, 88%) b.p. 120°-150° C. at 4 mmHg.

Provenance & Evidence