Formaldehyde → (+/-)-methyl (3aR,5S,6aR)-2-(phenylmethyl)hexahydro-2H-cyclopenta[d]isoxazole-5-carboxylate

Participants

Reaction Steps

To a solution of methyl-3-cyclopentene-1-carboxylate (6.1 g, 48.4 mmole) in toluene (150 mL) and EtOH (75 mL) was added paraformaldehyde (10.6 g, 242 mmole), N-hydroxybenzylamine hydrochloride (11.4 g, 72.6 mmole) and triethylamine (10.1 mL, 72.6 mmole). After 24 hours at 80° C., the reaction solution was concentrated under vacuum and redissolved in hexanes/EtOAc, 4:1 (200 mL) and filtered. The organic solution was concentrated and then purified on silica (hexanes/EtOAc, 4:1) to give the title compound (10.7 g, 85%) as a light yellow oil containing mixture of diastereoisomers in the ratio of 6 (trans) to 1 (cis): LC-MS (ES) m/e 262 (M+H)+.

Provenance & Evidence