Triethylamine → 6-Bromo-2-((R)-1-(4-methoxyphenyl)ethyl)-3-methylisoindolin-1-one

Participants

Reaction Conditions

Reaction Steps

Add solid methyl 5-bromo-2-(1-bromoethyl)benzoate (1724 g, 5.35 mol) to a solution of commercially available (R)-1-(4-methoxyphenyl)ethanamine (BePharm, WZG111219-071; 974 g, 6.44 mol) and triethylamine (1710 mL, 12.26 mol) in methanol (12 L). Heat the mixture for 10 hours at 67° C. then evaporate to dryness under reduced pressure. Partition the residue with ethyl acetate (5 L) and aqueous 1 N HCl (10 L), separate the phases, wash the organic phase again with aqueous 1 N HCl (5 L), saturated sodium bicarbonate, saturated aqueous sodium chloride, then dry over sodium sulfate, filter, and evaporate under reduced pressure. Dissolve the dark red oil in methyl-tert-butyl ether (750 mL) and add petroleum ether (3 L) with vigorous stirring. Filter the solids, wash with methyl-tert-butyl ether/petroleum ether (1:8), petroleum ether, dry in open air to give the title compound as an off-white solid (1014 g, 52%). ES/MS m/z: 360 (M+H).

Provenance & Evidence