Diisopropylamine → HCID 19097404, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (13.2 mL, 94 mmol) in THF (175 mL) at -60° C. under nitrogen was added n-BuLi (36.2 mL, 4 mmol, 2.6M hexane). The mixture was stirred for 30 minutes, cooled to -78° C. and ethyl 3,4,8-trimethyl-2-(phenylmethyl)-2-azabicyclo[2.2.2]octane-6-carboxylate (26.8 g, 85 mmol) in THF (225 mL) was added. The mixture was stirred for 3 hours, then ethyl chloroformate (8.96 mL, 94 mmol) in THF (20 mL) was added dropwise. The mixture was stirred for 24 hours, quenched with saturated NH4Cl, and poured into water (1000 mL). The solution was extracted with ether (3X), and the organic layers were combined and dried over MgSO4. The ether layer was treated with charcoal and the solvent was removed in vacuo to afford 32.1 g (97%) of diethyl 3,4,8-trimethyl-2-(phenylmethyl)-2-azabicyclo-[2.2.2] octane-6,6-dicarboxylate as a golden oil. The product was dissolved in ether and treated with ethereal HCl to afford 24 g (66%) of the hydrochloride salt as a white solid, m.p. 160°-162° C.

Provenance & Evidence