Methanol → HCID 131715390, compound

Participants

Reaction Steps

A mixture of 6.0 g (0.032 mole) of the title compound of Example 11 and 7.45 g (0.032 mole) of 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one in 150 mL of ethanol was heated to reflux under argon for 48 hours. The solvent was evaporated and the residue chromatographed on 500 g of silica gel (dry column) eluting with the lower phase of a mixture prepared by shaking 90 parts CHCl3, 30 parts CH3OH, 10 parts H2O, and 6 parts acetic acid. The fractions containing free base of the title compound were concentrated at 35°-50° C. on a rotary evaporator. The residue was dissolved in 500 mL of methylene chloride and neutralized to pH 10-11 with ice cold 1:1 NH4OH:H2O. The layers were separated and the organic phase was dried over Na2SO4 and concentrated. The residual solid was washed with hot ethanol and filtered. A sample of the free base, recrystallized from ethanol, had mp 183°-185° C. For the preparation of the HCl salt, the filter cake was suspended in 100 mL of ethanol and treated with about 10 mL of 5N HCl in ether. The solution was concentrated and allowed to cool, whereupon the hydrochloride salt of the title compound precipitated out. Two crops were collected, affording a total of 5.85 g of the hydrochloride salt of the title compound after drying at 100° C./1.0 mm overnight.

Provenance & Evidence