tert-butyl N-(6-bromohexyl)carbamate

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: Imidazole (70 mg) and 1.4 M sodium methoxide (1 ml) were added to N,N-dimethylformamide (3 ml) and the mixture was stirred at room temperature for 30 minutes. A solution of N-(tert-butoxycarbonyl)-6-bromo-hexylamine (280 mg) in N,N-dimethylformamide (1 ml) was added and after heating at 80-90° C. for 30 minutes stirring was continued overnight at room temperature. Evaporation in vacuo followed by stirring with acetone and fitration gave a filtrate which after evaporation was purified by chromatography on silica gel with ethyl acetate/methanol (4:1) as eluent to yield the title compound as a colourless oil. after heating at 80-90° C. for 30 minutes stirring was continued overnight at room temperature Evaporation in vacuo by stirring with acetone and fitration gave a filtrate which after evaporation was purified by chromatography on silica gel with ethyl acetate/methanol (4:1) as eluent

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Hydroxypyridine (262 mg) was added to a suspension of 60% sodium hydride (128 mg) in N,N-dimethylformamide (5 ml) and the mixture was stirred at 60° C. for 30 minutes. After cooling in ice a solution of N-(tert-butoxycarbonyl)-6-bromo-hexylamine (770 mg) (Helv. Chim. Acta 76 891 (1993) in N,N-dimethylformamide (3 ml) was added dropwise and stirring was continued overnight at room temperature. Ice and water were added and the mixture was extracted three times with diethyl ether. The organic phases were washed with saturated sodium chloride, dried and evaporated to leave a yellow oil which after purification by chromatography on silica gel with diethyl ether as eluent gave the desired compound as a colourless oil. stirring was continued overnight at room temperature the mixture was extracted three times with diethyl ether The organic phases were washed with saturated sodium chloride dried evaporated to leave a yellow oil which after purification by chromatography on silica gel with diethyl ether as eluent

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-(2-hydroxy-1-ethylcarbamoyl)-2-hydroxyquinoline (1.2 g), N-(tert-butoxycarbonyl)-6-bromo-hexylamine (2.2 g), cesium carbonate (4 g) and N,N-dimethylformamide (50 ml) was stirred for 6 hours at 60° C. followed by stirring overnight at room temperature. Ice and water were added and the mixture was extracted three times with ethyl acetate. The organic phases were washed with saturated sodium chloride, dried and evaporated to leave a yellow oil which after purification by chromatography on silica gel with ethyl acetate/methanol/aqueous ammonia (45:5:1.5) as eluent gave the desired compound as a light brown solid. by stirring overnight at room temperature the mixture was extracted three times with ethyl acetate The organic phases were washed with saturated sodium chloride dried evaporated to leave a yellow oil which after purification by chromatography on silica gel with ethyl acetate/methanol/aqueous ammonia (45:5:1.5) as eluent

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

Procedure: 0.5M Potassium bis-(trimethylsilyl)-amide in toluene (10 ml) was added dropwise at −30° C. in an argon atmosphere to a stirred solution of 2-oxo-1,2,3,4-tetrahydroquinoline (735 mg) in tetrahydrofuran (50 ml). After further cooling to −50° C. a solution of N-(tert-butoxycarbonyl)-6-bromo-hexylamine (1.5 g) in tetrahydrofuran (10 ml) was added slowly. Subsequently the temperature was allowed to raise to room temperature followed by heating at 50-60° C. for 48 hours. Ice and water were added and the mixture was extracted twice with ethyl acetate. The organic phases were washed with saturated sodium chloride, dried and evaporated to leave a yellow oil which after purification by chromatography on silica gel with ethyl acetate/hexane (1:1) as eluent gave the desired compound as a colourless oil. was added slowly by heating at 50-60° C. for 48 hours the mixture was extracted twice with ethyl acetate The organic phases were washed with saturated sodium chloride dried evaporated to leave a yellow oil which after purification by chromatography on silica gel with ethyl acetate/hexane (1:1) as eluent

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

Procedure: 0.5M Potassium bis-(trimethylsilyl)-amide in toluene (10 ml) was added dropwise at −30° C. in an argon atmosphere to a stirred solution of 2-oxo-1,2,3,4-tetrahydroquinoline (735 mg) in tetrahydrofuran (50 ml). After further cooling to −50° C. a solution of N-(tert-butoxycarbonyl)-6-bromo-hexylamine (1.5 g) in tetrahydrofuran (10 ml) was added slowly. Subsequently the temperature was allowed to raise to room temperature followed by heating at 50-60° C. for 48 hours. Ice and water were added and the mixture was extracted twice with ethyl acetate. The organic phases were washed with saturated sodium chloride, dried and evaporated to leave a yellow oil which after purification by chromatography on silica gel with ethyl acetate/hexane (1:1) as eluent gave the desired compound as a colourless oil. was added slowly by heating at 50-60° C. for 48 hours the mixture was extracted twice with ethyl acetate The organic phases were washed with saturated sodium chloride dried evaporated to leave a yellow oil which after purification by chromatography on silica gel with ethyl acetate/hexane (1:1) as eluent

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Hydroxyquinoline (640 mg) was added to a suspension of 600% sodium hydride (205 mg) in N,N-dimethylformamide (15 ml) and the mixture was stirred at 60° C. for 30 minutes. After cooling in ice a solution of N-(tert-butoxycarbonyl)-6-bromo-hexylamine (1.25 g) (Helv. Chim. Acta 76 891 (1993)) in N,N-dimethylformamide (10 ml) was added dropwise and stirring was continued overnight at room temperature. Ice and water were added and the mixture was extracted three times with ethyl acetate. The organic phases were washed with saturated sodium chloride, dried and evaporated to leave a yellow oil which after purification by chromatography on silica gel with ethyl acetate as eluent gave the desired compound as a colourless oil. was added dropwise stirring was continued overnight at room temperature the mixture was extracted three times with ethyl acetate The organic phases were washed with saturated sodium chloride dried evaporated to leave a yellow oil which after purification by chromatography on silica gel with ethyl acetate as eluent

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

Procedure: To a stirred solution of compound 2 (1 g, 4.61 mmol) in toluene (30 mL) were added Ph3P (1.81 g, 6.91 mmol) and CBr4 (2.29 g, 6.91 mmol) at RT under inert atmosphere and stirred for 3 h. The mixture was diluted with water (50 mL) and extracted with EtOAc (3×60 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude. The crude was purified (silica gel; 20% EtOAc/hexanes) to afford compound 3 (1 g, 78%) as colorless oil. 1H NMR (400 MHz, CDCl3): δ 4.51 (br s, 1H), 3.40 (t, J=6.8 Hz, 2H), 3.13-3.08 (m, 2H), 1.89-1.82 (m, 2H), 1.52-1.42 (m, 13H), 1.37-1.31 (m, 2H). extracted with EtOAc (3×60 mL) The combined organic extracts were dried over Na2SO4 filtered concentrated in vacuo to obtain the crude The crude was purified (silica gel; 20% EtOAc/hexanes)

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

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-hydroxybenzenesulfonamide (1.73 g, 10.0 mmol) and tert-butyl(6-bromohexyl)carbamate (2.1 g, 7.5 mmol) in acetonitrile (50 mL) was added anhydrous K2CO3 (2.07 g, 15 mmol). The reaction mixtures were stirred at 75° C. for overnight. Solvent was evaporated under reduced pressure to give a residue. The residue was diluted with 1 N HCl (40 mL), extracted with DCM, and dried over Na2SO4. Solvent was evaporated under reduce pressure to afford a residue, which was purified by biotage eluting with DCM to 10% MeOH in DCM to afford tert-butyl(6-(4-sulfamoylphenoxy)hexyl)carbamate (1.192 g, 43%). The reaction mixtures Solvent was evaporated under reduced pressure to give a residue extracted with DCM dried over Na2SO4 Solvent was evaporated to afford a residue, which was purified by biotage eluting with DCM to 10% MeOH in DCM

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-hydroxybenzenesulfonamide (1.73 g, 10.0 mmol) and tert-butyl(6-bromohexyl)carbamate (2.1 g, 7.5 mmol) in acetonitrile (50 mL) was added anhydrous K2CO3 (2.07 g, 15 mmol). The reaction mixtures were stirred at 75° C. for overnight. Solvent was evaporated under reduced pressure to give a residue. The residue was diluted with 1 N HCl (40 mL), extracted with DCM, and dried over Na2SO4. Solvent was evaporated under reduce pressure to afford a residue, which was purified by biotage eluting with DCM to 10% MeOH in DCM to afford tert-butyl(6-(4-sulfamoylphenoxy)hexyl)carbamate (1.192 g, 43%). The reaction mixtures Solvent was evaporated under reduced pressure to give a residue extracted with DCM dried over Na2SO4 Solvent was evaporated to afford a residue, which was purified by biotage eluting with DCM to 10% MeOH in DCM