4-phenoxybutanoyl chloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: As described for Example 235, a cis/trans mixture of N,N-dimethyl-1-phenylcyclohexane-1,4-diamine (800 mg) was reacted with 0.95 mg 4-phenoxybutyryl chloride and the crude product (1.48 g) was isolated analogously. By chromatography on silica gel (3.0×19 cm) with 100 ml diethyl ether followed by 400 ml diethyl ether/methanol (v:v=2:1), 450 mg of the more polar diastereoisomer of N-(4-dimethylamino-4-phenylcyclohexyl)-4-phenoxybutyramide were obtained and, as a solution in 5 ml 2-butanone and 5 ml ethyl acetate, were converted into the corresponding hydrochloride by addition of 21.3 μl water and 150 μl chlorotrimethylsilane (420 mg of a white solid, m.p. 191-192° C.). the crude product (1.48 g) was isolated analogously

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 238 g (1.2 mole) of 4-phenoxybutyryl chloride, dissolved in 350 ml of 1,2-dichloroethane, is added dropwise to a suspension, cooled to 0° C., of 192 g of aluminum trichloride in 1,200 ml of 1,2-dichloroethane within 4.5 hours while passing through nitrogen and stirring vigorously. The mixture is then stirred at 0° C. for 1.5 hours and allowed to warm to room temperature overnight. The mixture is added to a stirred mixture of 2,000 ml of concentrated hydrochloric acid and 2.5 kg of ice and then stirred for 1.5 hours. The aqueous phase is decanted off, and insoluble residue is removed from the organic phase by filtration, washing thoroughly with 1,2-dichloroethane. The aqueous phase is extracted 3-4 times more with methylene chloride, and the combined organic phases are washed with saturated sodium bicarbonate solution, water and saturated sodium chloride solution and dried over sodium sulfate. A yellowish oil is obtained after the solvent has been evaporated off in vacuo and is dissolved in diethyl ether, and the last residues of dyestuff are removed by filtration. Evaporation in vacuo results in a clear oil which distils at 74°-75° C./0.02 torr. is added dropwise to a suspension The mixture is then stirred at 0° C. for 1.5 hours stirred for 1.5 hours The aqueous phase is decanted off insoluble residue is removed from the organic phase by filtration washing thoroughly with 1,2-dichloroethane The aqueous phase is extracted 3-4 times more with methylene chloride the combined organic phases are washed with saturated sodium bicarbonate solution, water and saturated sodium chloride solution dried over sodium sulfate A yellowish oil is obtained after the solvent has been evaporated off in vacuo is dissolved in diethyl ether the last residues of dyestuff are removed by filtration Evaporation in vacuo results in a clear oil which distils at 74°-75° C./0.02 torr

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 252.3 g (1.40 mole) of 4-phenoxybutyric acid, 154 ml (2.1 mole) of thionyl chloride and a few drops of dimethylformamide are heated under reflux with exclusion of moisture. After evolution of gas has ceased (about 2 hours), the mixture is fractionated under water pump vacuum. The acid chloride distils at 149°-151° C. under reflux with exclusion of moisture (about 2 hours) The acid chloride distils at 149°-151° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: As described for Example 235, a cis/trans mixture of N,N-dimethyl-1-phenylcyclohexane-1,4-diamine (800 mg) was reacted with 0.95 mg 4-phenoxybutyryl chloride and the crude product (1.48 g) was isolated analogously. By chromatography on silica gel (3.0×19 cm) with 100 ml diethyl ether followed by 400 ml diethyl ether/methanol (v:v=2:1), 450 mg of the more polar diastereoisomer of N-(4-dimethylamino-4-phenylcyclohexyl)-4-phenoxybutyramide were obtained and, as a solution in 5 ml 2-butanone and 5 ml ethyl acetate, were converted into the corresponding hydrochloride by addition of 21.3 μl water and 150 μl chlorotrimethylsilane (420 mg of a white solid, m.p. 191-192° C.). the crude product (1.48 g) was isolated analogously