Reaction #60458

Reaction equation

bromomethylcyclobutane

cis-4-[3-(4,4-dimethylcyclohexyl)-4-piperazin-1-ylphenyl]-2,6-dimethylmorpholine

bromomethylcyclobutane

potassium carbonate

sodium hydrogencarbonate

→

cis-4-[4-(4-cyclobutylmethylpiperazin-1-yl)-3-(4,4-dimethylcyclohexyl)phenyl]-2,6-dimethylmorpholine

Solvents

ethyl acetate

dimethylformamide

Conditions

Workup

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 2 hours under the same conditions
3. 3
   WashThe separated organic layer was washed with water and brine in that order
4. 4
   workup.DISTILLATIONthe solvent was distilled off by nitrogen stream
5. 5
   OtherThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/hexane)

Procedure

A mixture of the cis-4-[3-(4,4-dimethylcyclohexyl)-4-piperazin-1-ylphenyl]-2,6-dimethylmorpholine (30 mg, 0.0778 mmol) produced in Example (61b), bromomethylcyclobutane (23 mg, 0.156 mmol), potassium carbonate (22 mg, 0.156 mmol) and dimethylformamide (1 mL) was stirred for 1 hour at an external temperature of 80° C. Then, bromomethylcyclobutane (23 mg, 0.156 mmol) was further added and stirring was continued for 2 hours under the same conditions. Saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture and extraction was performed with ethyl acetate. The separated organic layer was washed with water and brine in that order, and then the solvent was distilled off by nitrogen stream. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give cis-4-[4-(4-cyclobutylmethylpiperazin-1-yl)-3-(4,4-dimethylcyclohexyl)phenyl]-2,6-dimethylmorpholine as a colorless oil.

Source