tert-butyl N-[(4-fluoro-2-hydroxyphenyl)methyl]carbamate

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl 4-fluoro-2-hydroxybenzylcarbamate (Example 15; 12.2 mmol), 4-iodo-N-methylbutane-1-sulfonamide (Example 18; 18.3 mmol) and potassium carbonate (61 mmol) in DMF (60 ml) was stirred at 80° C. for 10 hours.

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

Procedure: Ethyl 5-bromopentanoate (14.9 mmol) was added dropwise over 15 minutes to a mixture of tert-butyl 4-fluoro-2-hydroxybenzylcarbamate (Example 15; 12.4 mmol) and potassium carbonate (16.1 mmol) in DMA (37 ml). The reaction was heated at 60° C. for 4 hours, followed by the addition of another amount of ethyl 5-bromopentanoate (4.5 mmol) and potassium carbonate (4.8 mmol) and heating at 60° C. for 2 hours. The solvent was evaporated. The residue was taken up in AcOEt and filtered. The filtrate was washed with AcOEt (×3) and concentrated in vacuo. The residue was purified by column chromategraphy over SiO2 (Hexanes/AcOEt, 8/1, v/v) to afford the target compound (4.1 gr, 96% purity). heating at 60° C. for 2 hours The solvent was evaporated filtered The filtrate was washed with AcOEt (×3) concentrated in vacuo The residue was purified by column chromategraphy over SiO2 (Hexanes/AcOEt, 8/1 v/v) to afford the target compound (4.1 gr, 96% purity)

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

Procedure: A solution of tert-butyl 2-(benzyloxy)-4-fluorobenzylcarbamate (Example 14; 9 mmol) in EtOH (80 ml) and ethyl acetate (240 ml) was treated with 1 atm of hydrogen at 25° C. over 10% Pd/C (0.4 gr) for 24 hours. The catalyst was removed by filtration through celite, washed with EtOH and the filtrate was concentrated to afford the title compound (2.2 g) as a yellow solid. The catalyst was removed by filtration through celite washed with EtOH the filtrate was concentrated

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

Procedure: A solution of tert-butyl 2-(benzyloxy)-4-fluorobenzylcarbamate (Example 14; 9 mmol) in EtOH (80 ml) and ethyl acetate (240 ml) was treated with 1 atm of hydrogen at 25° C. over 10% Pd/C (0.4 gr) for 24 hours. The catalyst was removed by filtration through celite, washed with EtOH and the filtrate was concentrated to afford the title compound (2.2 g) as a yellow solid. The catalyst was removed by filtration through celite washed with EtOH the filtrate was concentrated

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of tert-butyl 4-fluoro-2-hydroxybenzylcarbamate (Example 15; 12.2 mmol), 4-iodo-N-methylbutane-1-sulfonamide (Example 18; 18.3 mmol) and potassium carbonate (61 mmol) in DMF (60 ml) was stirred at 80° C. for 10 hours.

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

Procedure: Ethyl 5-bromopentanoate (14.9 mmol) was added dropwise over 15 minutes to a mixture of tert-butyl 4-fluoro-2-hydroxybenzylcarbamate (Example 15; 12.4 mmol) and potassium carbonate (16.1 mmol) in DMA (37 ml). The reaction was heated at 60° C. for 4 hours, followed by the addition of another amount of ethyl 5-bromopentanoate (4.5 mmol) and potassium carbonate (4.8 mmol) and heating at 60° C. for 2 hours. The solvent was evaporated. The residue was taken up in AcOEt and filtered. The filtrate was washed with AcOEt (×3) and concentrated in vacuo. The residue was purified by column chromategraphy over SiO2 (Hexanes/AcOEt, 8/1, v/v) to afford the target compound (4.1 gr, 96% purity). heating at 60° C. for 2 hours The solvent was evaporated filtered The filtrate was washed with AcOEt (×3) concentrated in vacuo The residue was purified by column chromategraphy over SiO2 (Hexanes/AcOEt, 8/1 v/v) to afford the target compound (4.1 gr, 96% purity)

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

Procedure: A solution of tert-butyl 2-(benzyloxy)-4-fluorobenzylcarbamate (Example 14; 9 mmol) in EtOH (80 ml) and ethyl acetate (240 ml) was treated with 1 atm of hydrogen at 25° C. over 10% Pd/C (0.4 gr) for 24 hours. The catalyst was removed by filtration through celite, washed with EtOH and the filtrate was concentrated to afford the title compound (2.2 g) as a yellow solid. The catalyst was removed by filtration through celite washed with EtOH the filtrate was concentrated