azepan-4-one;hydrochloride

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6 mL benzyl bromide was added to 5 g azepane-4-one hydrochloride and 18.5 g potassium carbonate in 50 mL THF and 25 mL water. The mixture was stirred 5 h at 50° C., evaporated, diluted with water and extracted with ethyl acetate. The organic layer was evaporated. The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2) to give 5 g of the desired product. Rf: 0.40 (hexane/ethyl acetate=1/1), (M+H)+=204 evaporated diluted with water extracted with ethyl acetate The organic layer was evaporated The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2)

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

Procedure: 20 g 5-Oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester was stirred over night at 110° C. in 200 mL 6 M hydrochloric acid. The reaction was concentrated to yield 11 g of the desired product. Rf: 0.20 (dichlormethane/methanol=9/1), (M+H)+=114 The reaction was concentrated

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

Procedure: 32 mL 62% HBr solution in 50 mL conc. acetic acid was added to 50 g hexahydro-azepin-4-on hydrochloride in 600 mL conc. acetic acid. Then 17.2 mL bromine in 50 mL conc. acetic acid was dropped to the reaction. The solvent was removed and the residue was crystallized from a mixture of DCM/MeOH (8/2) to give 79 g of the desired compound. The solvent was removed the residue was crystallized from a mixture of DCM/MeOH (8/2)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6 mL benzyl bromide was added to 5 g azepane-4-one hydrochloride and 18.5 g potassium carbonate in 50 mL THF and 25 mL water. The mixture was stirred 5 h at 50° C., evaporated, diluted with water and extracted with ethyl acetate. The organic layer was evaporated. The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2) to give 5 g of the desired product. Rf: 0.40 (hexane/ethyl acetate=1/1), (M+H)+=204 evaporated diluted with water extracted with ethyl acetate The organic layer was evaporated The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2)

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

Procedure: 20 g 5-Oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester was stirred over night at 110° C. in 200 mL 6 M hydrochloric acid. The reaction was concentrated to yield 11 g of the desired product. Rf: 0.20 (dichlormethane/methanol=9/1), (M+H)+=114 The reaction was concentrated

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

Procedure: 32 mL 62% HBr solution in 50 mL conc. acetic acid was added to 50 g hexahydro-azepin-4-on hydrochloride in 600 mL conc. acetic acid. Then 17.2 mL bromine in 50 mL conc. acetic acid was dropped to the reaction. The solvent was removed and the residue was crystallized from a mixture of DCM/MeOH (8/2) to give 79 g of the desired compound. The solvent was removed the residue was crystallized from a mixture of DCM/MeOH (8/2)

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

Procedure: 27 mL 33% HBr solution was added to 20 g hexahydro-azepin-4-one hydrochloride in 225 mL conc. acetic acid. Subsequently 6.9 mL bromine in 25 mL conc. acetic acid was added dropwise to the reaction mixture and the mixture was stirred 30 min at RT. The solvent was removed and the residue was crystallized with acetonitrile to give 27.9 g of the desired compound. The solvent was removed the residue was crystallized with acetonitrile

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

Procedure: 27 mL 33% HBr solution was added to 20 g hexahydro-azepin-4-one hydrochloride in 225 mL conc. acetic acid. Subsequently 6.9 mL bromine in 25 mL conc. acetic acid was added dropwise to the reaction mixture and the mixture was stirred 30 min at RT. The solvent was removed and the residue was crystallized with acetonitrile to give 27.9 g of the desired compound. The solvent was removed the residue was crystallized with acetonitrile

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

Procedure: 260 ml of 33% hydrogen bromide/glacial acetic acid solution are added at ambient temperature, with stirring, to a solution of 130 g (0.87 mol) of hexahydro-4H-azepin-4-one-hydrochloride (melting point: 177°-178° C.) in 975 ml of glacial acetic acid. Then, within 1.5 hours, a solution of 44.6 ml=139 g (0.87 mol) of bromine in 260 ml of glacial acetic acid is added dropwise, with stirring, at ambient temperature and the resulting mixture is stirred for a further 1.5 hours at ambient temperature. It is evaporated down to dryness in vacuo, the evaporation residue is dissolved in about 1 litre of acetone, mixed with about 0.2 litres of ethyl acetate and left to crystallise out. It is filtered through a glass frit and the filter cake is washed with about 0.2 1 of ice cold acetone. It is then dried at 80° C. in a circulating air dryer. Yield: 214 g (90% of theory), Melting point: 140°-145° C. the resulting mixture is stirred for a further 1.5 hours at ambient temperature It is evaporated down to dryness in vacuo the evaporation residue is dissolved in about 1 litre of acetone mixed with about 0.2 litres of ethyl acetate left to crystallise out It is filtered through a glass frit the filter cake is washed with about 0.2 1 of ice cold acetone It is then dried at 80° C. in a circulating air dryer

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

Procedure: 260 ml of 33% hydrogen bromide/glacial acetic acid solution are added at ambient temperature, with stirring, to a solution of 130 g (0.87 mol) of hexahydro-4H-azepin-4-one-hydrochloride (melting point: 177°-178° C.) in 975 ml of glacial acetic acid. Then, within 1.5 hours, a solution of 44.6 ml=139 g (0.87 mol) of bromine in 260 ml of glacial acetic acid is added dropwise, with stirring, at ambient temperature and the resulting mixture is stirred for a further 1.5 hours at ambient temperature. It is evaporated down to dryness in vacuo, the evaporation residue is dissolved in about 1 litre of acetone, mixed with about 0.2 litres of ethyl acetate and left to crystallise out. It is filtered through a glass frit and the filter cake is washed with about 0.2 1 of ice cold acetone. It is then dried at 80° C. in a circulating air dryer. Yield: 214 g (90% of theory), Melting point: 140°-145° C. the resulting mixture is stirred for a further 1.5 hours at ambient temperature It is evaporated down to dryness in vacuo the evaporation residue is dissolved in about 1 litre of acetone mixed with about 0.2 litres of ethyl acetate left to crystallise out It is filtered through a glass frit the filter cake is washed with about 0.2 1 of ice cold acetone It is then dried at 80° C. in a circulating air dryer

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

Procedure: 32.2 mL (0.37 mol) Hydrobromic acid (62%) in 50 mL acetic acid were added dropwise to 50.0 g (0.33 mol) hexahydro-4H-azepin-4-one hydrochloride in 0.6 L acetic acid. 17 mL (0.34 mol) bromine in 50 mL acetic acid were added dropwise and the reaction was stirred at room temperature (RT). Then reaction was concentrated and the residue was crystallized with acetonitrile. Then reaction was concentrated the residue was crystallized with acetonitrile

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6 mL benzyl bromide was added to 5 g azepane-4-one hydrochloride and 18.5 g potassium carbonate in 50 mL THF and 25 mL water. The mixture was stirred 5 h at 50° C., evaporated, diluted with water and extracted with ethyl acetate. The organic layer was evaporated. The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2) to give 5 g of the desired product. Rf: 0.40 (hexane/ethyl acetate=1/1), (M+H)+=204 evaporated diluted with water extracted with ethyl acetate The organic layer was evaporated The residue was purified by chromatographie on silica gel (petrolether/ethyl acetate:8/2)