BENZETIMIDE synthesis

Yield:-

Reaction Conditions:

in ethanol;n-heptanePurification / work up;Resolution of racemate;

Steps:

A.A9.a
Example A9; a) Preparation of intermediate 34 and intermediate 34a; Intermediate 34 Intermediate 34a; NaHCO₃ (0.5 mol) was dissolved in H₂O (350 ml). This solution was added to a mixture of benzetimide hydrochloride (0.209 mol) in DCM (400 ml). The reaction mixture was stirred for 18 hours at room temperature. The organic layer was separated, dried (MgSO₄), filtered and the solvent was evaporated. Ethanol was added and co- 5 evaporated. The residue was separated into its enantiomers by chiral column chromatography over an OJ column (eluent: ethanol/heptane 60/40). Two product fraction groups were collected and their solvent was partially evaporated (to a +/- 150 ml concentrate). Crystallization occurred in each concentrate. Each precipitate was filtered off, washed with ethanol, and dried (vacuum, 50 ⁰C). Yield : 21.2g of intermediate 34a 0 (S configuration) and 27.0 g of intermediate 34 (R configuration).

References:

JANSSEN PHARMACEUTICA N.V. WO2007/90826, 2007, A1 Location in patent:Page/Page column 65