3-Oxocyclobutane-1-carboxylic acid → 3-(3-Fluoro-4-(pyrrolidin-1-ylmethyl)phenyl)-3-hydroxycyclobutanecarboxylic acid

Participants

Reaction Steps

n-Butyllithium (2.5M/hexanes, 78 ml, 0.195 mol) was added down the reaction flask walls over 5 min to a −78° C. solution of 1-(4-bromo-2-fluorobenzyl)pyrrolidine (50.0 g, 0.194 mol) in THF (500 mL). After stirring at −78° C. for 1 h, a −78° C. solution of 3-oxocyclobutanecarboxylic acid (11.0 g, 96.4 mmol) in THF (150 mL) was cannulated over 10 min into the reaction mixture. The resulting dark orange solution was slowly warmed to room temperature over 16 h. LC/MS of the mixture showed the title compound 294.2 (M+H). This material was used as a crude solution without work-up, assuming ˜0.12 M concentration of the title compound.

Provenance & Evidence