Chloroacetamide → 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 (0.68 g, 1.5 mmoles) (prepared in Example 61, Step A) was added to a stirred suspension of sodium hydride (60 mg, 1.5 mmole of 60% emulsion, washed with petroleum ether) in acetonitrile (10 ml) followed by tetrabutylammonium bromide (0.48 g, 1.5 mmole). The reaction mixture was heated to 40° C. for 15 minutes to obtain a clear solution and treated with chloroacetamide (0.56 g, 6 mmoles) potassium iodide (0.25 g) and heated to reflux. The solvent was evaporated and the residue was partitioned between ethyl acetate and water. The residue from the organic layer was chromatographed over deactivated silica using methylene chloride (100), methanol (2), ammonia (0.5) solvent system. The appropriate fractions were combined and the residue (0.2 g) was crystallized from ethanol-water to yield the title compound (60 mg), mp. 173°-175° C.

Provenance & Evidence