Fred Ward for the preparation of intermediates . Spnthesis and Analgetic Activity of Some 1 - Substituted 3 - Pyrrolidinylanilides and Dihydrobenzoxazinones

3,4,5,6-Tetrahydro-1[2-(4-hydroxy-4-phenyl-l-piperidyl)ethyl] -l-benzazocin-2( 1H)-one Hydrochloride (21).-To 10.0 g (0.057 mole) of 3,4,5,6-tetrahydrobenzazocin-2( lH)-one in 100 ml of xylene was carefully added 3.0 g of NaH with stirring. The reaction mixture was then refluxed with stirring for 2 hr. To the mixture was added 3.0 g of NaH and 19.2 g (0.06 mole) of 1-(2-chlorethyl)-4-hydroxy-4-phenylpiperidine hydrobromide. The reaction mixture was stirred under reflux for 8 hr, then treated with HzO and CHC13. The organic solvents xere concentrated in vacuo leaving an oily residue. The starting amide was removed by vacuum distillation; the remaining residue weighed 17.0 g. The hydrochloride was prepared by adding exce.r HC1 in 2-PrOH to a solution of the base in 3IeOH. Upon addition of EtlO, a solid formed which was recrystallized three timei from 3IeOH-EtzO; yield 3.5 g, mp 237-238". 1 [ 34 4-p-Fluorophenyl-1 -piperazyl)propyl] -3,4-dihydro-7hydroxycarbostyril Hemioxalate (15).-To 15.0 g (0.032 mole) of 7-benzyloxy-1[ 3-( 4-p-fluorophenyl-l-piperazyl)propyl] -3,4dihydrocarbostyril in 200 ml of absolute EtOH was added 2.5 g of 10% Pd-C and the mixture was hydrogenated at 3.5 kg/cmZfor 2 hr. The solution was filtered to remove the catalyst and the filtrate was concentrated in vacuo leaving an oil. The oxalate was prepared by adding 3.0 g (0.034 mole) of oxalic acid in Et20 to 13.0 g (0.034 mole) of the free base. A solid material was obtained which was recrystallized from NeOH-Et20; yield 5.0 g, mp 209-210".