Trifluoroacetic acid → (+/-)-(trans)-(4-Azetidin-1-yl-piperidin-3-yl)-methanol

Participants

Reaction Steps

To a solution of 4-azetidin-1-yl-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (373 mg, 1.25 mmol) in anhydrous DCM (10 mL) was slowly added a solution of diisobutylaluminum hydride in hexanes (1M, 3.8 mL, 3.8 mmol) at −70° C. The reaction mixture was allowed to warm to −10° C. over 90 min, then stirred at RT for 15 min. Water was added to the reaction mixture before being loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH then eluted with 2 M NH3 in MeOH to give 4-azetidin-1-yl-3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester. To a solution of 4-azetidin-1-yl-3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester in DCM (10 mL) was added TFA (1 mL) and the resulting mixture was stirred at RT for 30 min. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then eluted with 2 M NH3 in MeOH to give a 1:1 cis:trans mixture of the title compound as a colourless oil (188 mg, 88%).

Provenance & Evidence