Acetonitrile → Cis-4-amino-2-(2-amino-2-oxoethoxy)-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl}benzamide sesquihydrate

Participants

Reaction Conditions

Reaction Steps

Cis-4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]3-methoxy-4-piperidinyl}-2-hydroxybenzamide (1.35 g, 3 mmoles) (prepared in Example 61, Step A) was added to a stirred suspension of sodium hydride (0.12 g, 3 mmoles of 60% emulsion, washed with petroleum ether) in acetonitrile (20 ml) followed by tetrabutylammonium bromide (0.96 g, 3 mmoles). The reaction mixture was heated to 40° C. for 15 minutes and then treated with methyl bromoacetate (0.92 g, 6 mmoles). After stirring for 2 days the reaction mixture was partitioned between water and ethyl acetate. The organic phase was dried, concentrated in vacuo and the residue was chromatographed over deactivated silica using a methylene chloride (100), methanol (2), ammonia (0.5) solvent system. The appropriate fractions were combined and the solvent evaporated. The residue was dissolved in methylene chloride by adding methanol and the solution was saturated with gaseous ammonia in the cold. After 30 minutes the solvent was evaporated and the residue crystallized from ethanol-water to yield 0.3 g of the title compound as a sesquihydrate (19%), mp. 173°-175° C.

Provenance & Evidence