3-azabicyclo[3.1.0]hexane-2,4-dione

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Diethyl azodicarboxylate (0.94 g) was added to a mixture of 3-azabicyclo[3.1.0]hexane-2,4-dione (0.5 g), 1,7-heptanediol (2.46 g), triphenylphosphine (1.42 g) and 4 angstrom sieves (1.5 g) in dry tetrahydrofuran (10 ml) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 days and was then filtered. The solids were washed with ethyl acetate (2×50 ml) and the combined filtrates were evaporated in vacuo. The residue was purified by chromatography on silica using 60-70% ethyl acetate/hexane as eluant, followed by kugelrohr distillation (b.p. 200-220° C. @ 1 mmHg) to give the subtitle compound as a viscous oil. was then filtered The solids were washed with ethyl acetate (2×50 ml) the combined filtrates were evaporated in vacuo The residue was purified by chromatography on silica using 60-70% ethyl acetate/hexane as eluant followed by kugelrohr distillation (b.p. 200-220° C. @ 1 mmHg)

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

Procedure: Diethyl azodicarboxylate (0.5 g) was added dropwise over 1 minute to a stirred solution of triphenylphosphine (0.75 g) in tetrahydrofuran (20 ml) at -78° C. under a nitrogen atmosphere. The reaction mixture was stirred for 5 minutes and then 6-hepten-1-ol (0.36 g) was added dropwise over 1 minute, followed by stirring at -78° C. for a further 5 minutes. Neopentanol (0.12 g) was added to the reaction mixture, followed by 3-azabicyclo[3.1.0]hexane-2,4dione (0.32 g) and stirring was continued for a further 5 minutes at -78° C. The reaction mixture was warmed to room temperature and stirred overnight. The volatiles were removed by evaporation in vacuo and the residue was triturated with hexane/dichloromethane and then filtered. The filtrate was evaporated in vacuo and then purified by chromatography on silica gel using 20% ethyl acetate/hexane as eluant. The title compound was obtained as a colourless oil (boiling point 150-160° C. @ 1 mmHg). by stirring at -78° C. for a further 5 minutes stirring was continued for a further 5 minutes at -78° C stirred overnight The volatiles were removed by evaporation in vacuo the residue was triturated with hexane/dichloromethane filtered The filtrate was evaporated in vacuo purified by chromatography on silica gel using 20% ethyl acetate/hexane as eluant

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

Procedure: Sodium hydride (0.11 g) was added to a solution of 3-azabicyclo[3.1.0]hexane-2,4-dione (0.3 g) and 2-bromooctane (0.52 g) in dimethylformamide (5 ml) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 48 hours. The mixture was diluted with water (15 ml) and then extracted with toluene (20 ml). The organic extract was washed with water (15 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by Kugelrohr distillation (boiling point 130-140° C. @ 0.1 mmHg) to give the title compound as a colourless oil. extracted with toluene (20 ml) The organic extract was washed with water (15 ml) dried (MgSO4) evaporated in vacuo The residue was purified by Kugelrohr distillation (boiling point 130-140° C. @ 0.1 mmHg)

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

Procedure: Sodium hydride (0.11 g) was added to a solution of 3-azabicyclo[3.1.0]hexane-2,4-dione (0.3 g) in dry tetrahydrofuran (10 ml) under a nitrogen atmosphere at room temperature. The suspension was stirred for 5 minutes and 1-iodo-3-methylbutane (0.53 g) was then added in one portion to the reaction mixture. After stirring for two hours at room temperature, dimethylformamide (5 ml) was added and the reaction mixture was stirred for a further 16 hours at room temperature. The reaction mixture was diluted with dichloromethane and then partitioned with water (20 ml). The aqueous phase was extracted with dichloromethane (20 ml) and the combined organic extracts were washed with water (2×20 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by chromatography on silica gel (50 g) using 25% ethyl acetate/hexane as eluant to give the title compound as a colourless oil. After stirring for two hours at room temperature the reaction mixture was stirred for a further 16 hours at room temperature partitioned with water (20 ml) The aqueous phase was extracted with dichloromethane (20 ml) the combined organic extracts were washed with water (2×20 ml) dried (MgSO4) evaporated in vacuo The residue was purified by chromatography on silica gel (50 g)

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

Procedure: Sodium hydride (0.11 g) was added to a solution of 3-azabicyclo[3.1.0]hexane-2,4dione (0.3 g) and 7-octenyl bromide (0.52 g) in dimethylformamide (5 ml) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. The mixture was diluted with water (15 ml) and then extracted with toluene (20 ml). The organic extract was washed with water (15 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by Kugelrohr distillation (boiling point 130-140° C. @ 0.1 mmHg) to give the title compound as a colourless oil. extracted with toluene (20 ml) The organic extract was washed with water (15 ml) dried (MgSO4) evaporated in vacuo The residue was purified by Kugelrohr distillation (boiling point 130-140° C. @ 0.1 mmHg)

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

Procedure: Sodium hydride (0.11 g) was added to a solution of 3-azabicyclo[3.1.0]hexane-2,4-dione (0.3 g) and 1-bromo-2-ethylhexane (0.52 g) in dimethylformamide (5 ml) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. The mixture was diluted with water (15 ml) and then extracted with toluene (20 ml). The organic extract was washed with water (15 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by Kugelrohr distillation (boiling point 140-160° C. @ 0.1 mmHg) to give the title compound as a colourless oil. extracted with toluene (20 ml) The organic extract was washed with water (15 ml) dried (MgSO4) evaporated in vacuo The residue was purified by Kugelrohr distillation (boiling point 140-160° C. @ 0.1 mmHg)

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

Procedure: Sodium hydride (0.11 g) was added to a solution of 3-azabicyclo[3.1.0]hexane-2,4dione (0.3 g) and 1-bromo-2-cyclohexylethane (0.52 g) in dimethylformamide (5 ml) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 16 hours. The mixture was diluted with water (15 ml) and then extracted with toluene (20 ml). The organic extract was washed with water (15 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by Kugelrohr distillation (boiling point 130-140° C. @ 0.1 mmHg) to give the title compound as a colourless oil. extracted with toluene (20 ml) The organic extract was washed with water (15 ml) dried (MgSO4) evaporated in vacuo The residue was purified by Kugelrohr distillation (boiling point 130-140° C. @ 0.1 mmHg)

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

Procedure: Sodium hydride (0.11 g) was added to a solution of 3-azabicyclo[3.1.0]hexane-2,4-dione (0.3 g) in dry tetrahydrofuran (10 ml) under a nitrogen atmosphere at room temperature. The suspension was stirred for 5 minutes and 1-iodoheptane (0.61 g) was then added in one portion to the reaction mixture. After stirring for two hours at room temperature, dimethylformamide (5 ml) was added and the reaction mixture was stirred for a further 16 hours at room temperature. The reaction mixture was diluted with dichloromethane and then partitioned with water (20 ml). The aqueous phase was extracted with dichloromethane (20 ml) and the combined organic extracts were washed with water (2×20 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by chromatography on silica gel (50 g) using 25-30% ethyl acetate/hexane as eluant to give the title compound as a colourless oil. After stirring for two hours at room temperature the reaction mixture was stirred for a further 16 hours at room temperature partitioned with water (20 ml) The aqueous phase was extracted with dichloromethane (20 ml) the combined organic extracts were washed with water (2×20 ml) dried (MgSO4) evaporated in vacuo The residue was purified by chromatography on silica gel (50 g)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (1.48 g, 60% in oil) was added to a stirred solution of 3-azabicyclo[3.1.0]hexane-2,4-dione (4.0 g) and 1-iodooctane (8.88 g) in dry dimethylformamide (70 ml) under a nitrogen atmosphere at 0° C. The reaction mixture was stirred at 0° C. for a further 30 minutes and then at room temperature for 16 hours. The mixture was diluted with water (100 ml) and then extracted with ether (150 ml). The organic extract was washed with water (2×70 ml), dried (MgSO4) and evaporated in vacuo to leave a brown oil. The oil was purified by distillation in vacuo (boiling point 146-147° C. @ 0.1 mmHg) to give the title compound as a pale yellow oil. at room temperature for 16 hours extracted with ether (150 ml) The organic extract was washed with water (2×70 ml) dried (MgSO4) evaporated in vacuo to leave a brown oil The oil was purified by distillation in vacuo (boiling point 146-147° C. @ 0.1 mmHg)