2-phenylcyclohex-2-en-1-one

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

Procedure: A suspension of 4.97 g (19.6 mmole) of 2-bromo-6-phenylcyclohexanone in 120 mL of di-n-butyl ether was heated at 175° C. for 7 hours, at which point evolution of gaseous HBr had essentially ceased. The mixture was concentrated in vacuo and the residue purified by flash chromatography with 75:25 methylene chloride: hexanes to provide 2.69 g (80%) of a white solid. The mixture was concentrated in vacuo the residue purified by flash chromatography with 75:25 methylene chloride

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

Procedure: A suspension of 4.97 g (19.6 mmole) of 2-bromo-6-phenylcyclohexanone in 120 mL of di-n-butyl ether was heated at 175° C. for 7 hours, at which point evolution of gaseous HBr had essentially ceased. The mixture was concentrated in vacuo and the residue purified by flash chromatography with 75:25 methylene chloride: hexanes to provide 2.69 g (80%) of a white solid. The mixture was concentrated in vacuo the residue purified by flash chromatography with 75:25 methylene chloride

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

Procedure: When phenylmagnesium bromide (a) or phenyllithium (b) is used in place of 3-pyridylmagnesium bromide, the phenylcarbinol enol ether 13 arises (Scheme 3). This is refluxed with acetic anhydride (c) or dehydrated with phosphorous oxychloride and pyridine (d) and hydrolyzed with aqueous hydrochloric acid (e) to give 2-phenyl-2-cyclohexenone (14). Reduction of 14 with sodium borohydride and cerium chloride in methanol (f) provides the allylic alcohol 15 which is dehydrated (d) to 2-phenyl-1,3-cyclohexadiene 16. Reaction of 16 with tertiary butyl nitrosoformate (2) as in Scheme 1, provides the Diels-Alder cycloadduct 17, which can be converted in four steps to (±) exo-2-phenyl-7-azabicyclo[2.2.1]heptane (18), the phenyl analog of epibatidine. ##STR6##

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

Procedure: When phenylmagnesium bromide (a) or phenyllithium (b) is used in place of 3-pyridylmagnesium bromide, the phenylcarbinol enol ether 13 arises (Scheme 3). This is refluxed with acetic anhydride (c) or dehydrated with phosphorous oxychloride and pyridine (d) and hydrolyzed with aqueous hydrochloric acid (e) to give 2-phenyl-2-cyclohexenone (14). Reduction of 14 with sodium borohydride and cerium chloride in methanol (f) provides the allylic alcohol 15 which is dehydrated (d) to 2-phenyl-1,3-cyclohexadiene 16. Reaction of 16 with tertiary butyl nitrosoformate (2) as in Scheme 1, provides the Diels-Alder cycloadduct 17, which can be converted in four steps to (±) exo-2-phenyl-7-azabicyclo[2.2.1]heptane (18), the phenyl analog of epibatidine. ##STR6##

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

Procedure: A suspension of 4.97 g (19.6 mmole) of 2-bromo-6-phenylcyclohexanone in 120 mL of di-n-butyl ether was heated at 175° C. for 7 hours, at which point evolution of gaseous HBr had essentially ceased. The mixture was concentrated in vacuo and the residue purified by flash chromatography with 75:25 methylene chloride: hexanes to provide 2.69 g (80%) of a white solid. The mixture was concentrated in vacuo the residue purified by flash chromatography with 75:25 methylene chloride

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

Procedure: When phenylmagnesium bromide (a) or phenyllithium (b) is used in place of 3-pyridylmagnesium bromide, the phenylcarbinol enol ether 13 arises (Scheme 3). This is refluxed with acetic anhydride (c) or dehydrated with phosphorous oxychloride and pyridine (d) and hydrolyzed with aqueous hydrochloric acid (e) to give 2-phenyl-2-cyclohexenone (14). Reduction of 14 with sodium borohydride and cerium chloride in methanol (f) provides the allylic alcohol 15 which is dehydrated (d) to 2-phenyl-1,3-cyclohexadiene 16. Reaction of 16 with tertiary butyl nitrosoformate (2) as in Scheme 1, provides the Diels-Alder cycloadduct 17, which can be converted in four steps to (±) exo-2-phenyl-7-azabicyclo[2.2.1]heptane (18), the phenyl analog of epibatidine. ##STR6##

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

Procedure: A mixture of 2-phenyl-2-cyclohexen-1-one (0.6 g, 3.5 mmol, Tetrahedron 1972, 28, 2369), hydroxylammonium chloride (0.5 g, 7 mmol) and dry pyridine (15 ml) was heated at reflux for 3 h. The reaction mixture was allowed to cool and the solvent was evaporated in vacuo. The residue was dissolved in a mixture of ethyl acetate and water. A 10% citric acid solution was added until acidic pH and the phases were separated. The organic phase was extracted with a 10% citric acid solution and dried (MgSO4). The solvent was evaporated in vacuo to give 0.55 g of 2-phenyl-2-cyclohexen-1 -one oxime. M.p. 144°-146° C. was heated at reflux for 3 h to cool the solvent was evaporated in vacuo The residue was dissolved in a mixture of ethyl acetate and water A 10% citric acid solution was added until acidic pH the phases were separated The organic phase was extracted with a 10% citric acid solution dried (MgSO4) The solvent was evaporated in vacuo

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

Procedure: When phenylmagnesium bromide (a) or phenyllithium (b) is used in place of 3-pyridylmagnesium bromide, the phenylcarbinol enol ether 13 arises (Scheme 3). This is refluxed with acetic anhydride (c) or dehydrated with phosphorous oxychloride and pyridine (d) and hydrolyzed with aqueous hydrochloric acid (e) to give 2-phenyl-2-cyclohexenone (14). Reduction of 14 with sodium borohydride and cerium chloride in methanol (f) provides the allylic alcohol 15 which is dehydrated (d) to 2-phenyl-1,3-cyclohexadiene 16. Reaction of 16 with tertiary butyl nitrosoformate (2) as in Scheme 1, provides the Diels-Alder cycloadduct 17, which can be converted in four steps to (±) exo-2-phenyl-7-azabicyclo[2.2.1]heptane (18), the phenyl analog of epibatidine. ##STR6##

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

Procedure: A suspension of 4.97 g (19.6 mmole) of 2-bromo-6-phenylcyclohexanone in 120 mL of di-n-butyl ether was heated at 175° C. for 7 hours, at which point evolution of gaseous HBr had essentially ceased. The mixture was concentrated in vacuo and the residue purified by flash chromatography with 75:25 methylene chloride: hexanes to provide 2.69 g (80%) of a white solid. The mixture was concentrated in vacuo the residue purified by flash chromatography with 75:25 methylene chloride