(1R,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-one

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

Procedure: To pseudo-pelletierine (1.5 g, 9.8 mmol) in toluene (75 mL) was added pyrrolidine (4.9 mL, 58.75 mmol). TiCl4 (0.66 mL, 6.0 mmol) in toluene (10 mL) was then added to the mixture at −5° C. The reaction mixture was left to warm up to rt and stirred for 2 days. The mixture was filtered and the filtrate was concentrated to a residue and toluene (100 mL) was added and the mixture was filtered again. The filtrate was concentrated to a residue to afford the product (2.0 g, 100%) as yellow oil. The reaction mixture was left The mixture was filtered the filtrate was concentrated to a residue and toluene (100 mL) was added the mixture was filtered again The filtrate was concentrated to a residue

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

Procedure: Accordingly, phenylhydrazine or 4-fluorophenylhydrazine is condensed with nortropinone or pseudo-pelletierine (9-azabicyclo-[3.2.1]nonan-3-one) under conditions of the Fischer indole synthesis to afford 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole or 6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indole or the corresponding-2-fluoro derivatives. Alkylation of the basic nitrogen in these compounds with the appropriately substituted alkyl halide or tosylate in dimethylformamide affords the compounds of Formula I wherein R1 is hydrogen. Alternatively, compounds of Formula I may be obtained by acylation of the hexahydro-7,10-iminocyclohept[b]indole or hexahydro-7,11-imino-5H-cyclooct[b]indole followed by reduction of the resulting amide with, for example, lithium aluminum hydride. Compounds of Formula I in which R1 is other than hydrogen or phenyl are prepared by abstraction of the a proton from the indole nitrogen, for example with sodium hydride in dimethylformamide, followed by reaction of the resulting anion with the required alkyl or aralkyl halide. Compounds of Formula I in which R1 is phenyl are prepared by alkylation or acylation/reduction of 5-phenyl-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept-[b]indole (J. G. Berger and P. Tahbaz, U.S. Pat. No. 4,360,673, Nov. 23, 1982) or 5-phenyl-6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indole as outlined above.

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

Procedure: To pseudo-pelletierine (1.5 g, 9.8 mmol) in toluene (75 mL) was added pyrrolidine (4.9 mL, 58.75 mmol). TiCl4 (0.66 mL, 6.0 mmol) in toluene (10 mL) was then added to the mixture at −5° C. The reaction mixture was left to warm up to rt and stirred for 2 days. The mixture was filtered and the filtrate was concentrated to a residue and toluene (100 mL) was added and the mixture was filtered again. The filtrate was concentrated to a residue to afford the product (2.0 g, 100%) as yellow oil. The reaction mixture was left The mixture was filtered the filtrate was concentrated to a residue and toluene (100 mL) was added the mixture was filtered again The filtrate was concentrated to a residue

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

Procedure: 186.8 g of pseudo-pelletierine and 264 g of freshly distilled chloroformic acid ethyl ester are slowly heated to a boil in 1 liter of absolute toluene within one hour. A vigorous evolution of gas sets in. The mixture is heated to a boil under reflux for a further 16 hours, then cooled and filtered. The filtrate is concentrated in a vacuum, and the residue is purified through vacuum distillation to obtain 223 g (86.5 percent) of light-yellow oil (b.p. 101° C. at 2.7 Pa.) The mixture is heated to a boil under reflux for a further 16 hours cooled filtered The filtrate is concentrated in a vacuum the residue is purified through vacuum distillation