tert-Butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate → tert-butyl (3R)-4-[2-(3-cyano-4-fluoro-2-methylphenyl)-2-hydroxyethyl]-3-(hydroxymethyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

6-Fluoro-2-methyl-3-(oxiran-2-yl)benzonitrile (prepared as described above for I-17A and I-17B, Method 1, Steps A-C) (4.80 g, 27.1 mmol) and (R)-4-N-BOC-2-hydroxymethyl-piperazine (commercially available, e.g. from Acesys Pharmatech, catalog #A1612R; and also described in J. Org. Chem., 2007, 72(22), p. 8591-8592) (8.79 g. 40.6 mmol) were suspended in EtOH (30 mL) and heated in a microwave apparatus at 150° C. for 1 h. The reaction mixture was cooled and evaporated to dryness. The residue was purified by chromatography through a 330 g ISCO Redi-sep column eluting with ethyl acetate to 5% MeOH/ethyl acetate gradient to yield the title compound. LC-MS: M+1=394;

Provenance & Evidence