Diisopropylamine → 1,1-Dimethylethyl 3-cyano-3-(hydroxymethyl)-1-azetidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of N-isopropylpropan-2-amine (11.54 mL) in THF (50 mL) was added dropwise a solution of n-butyllithium in hexane (1.6 M, 51.45 mL) at −78° C. The reaction mixture was warmed to 0° C. and then stirred for 30 minutes. The reaction mixture was cooled to −78° C. again, and then a solution of tert-butyl 3-cyanoazetidine-1-carboxylate (5.0 g) in THF (30 mL) was added dropwise, followed by stirring at −78° C. for 1 hour. To the reaction mixture was added dropwise a solution of 1H-benzotriazol-1-yl-methanol (8.19 g) in THF (20 mL) at −78° C., followed by stirring at −78° C. for 3 hours. To the reaction mixture was added a saturated aqueous NH4Cl solution (100 mL), followed by extraction with EtOAc (50 mL) three times. The organic layer was washed with brine, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (automatic purification device, hexane:EtOAc=100:0 to 50:50) to obtain tert-butyl 3-cyano-3-(hydroxymethyl)azetidine-1-carboxylate (5.68 g) as a white solid.

Provenance & Evidence