1-(5-bromo-2-fluorophenyl)propan-1-ol

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

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

Procedure: A mixture of 10 g (42.9 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanol (Example 3A), 8.75 g (85.8 mmol) neutral aluminium oxide and 18.5 g (85.8 mmol) pyridinium chlorochromate in dichloromethane (100 ml) was stirred at room temperature for 4 h. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml). The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (8.6 g, 87% of th.) was used in the next step without further purification. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml) The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a solution of 15 g (73.9 mmol) 5-bromo-2-fluorobenzaldehyde in diethyl ether (100 ml) at 0° C. were slowly added 27.1 ml (81.3 mmol) of ethyl magnesium bromide (3 M solution in diethyl ether). After stirring at 0° C. for 3 h, water (20 ml) was carefully added upon which a white precipitate formed. The solid was filtered off and washed with tert-butylmethyl ether. The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (16.1 g, 93% of th.) was used in the next step without further purification. at 0° C. formed The solid was filtered off washed with tert-butylmethyl ether The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: A mixture of 10 g (42.9 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanol (Example 5A), 8.75 g (85.8 mmol) neutral aluminium oxide and 18.5 g (85.8 mmol) pyridinium chlorochromate in dichloromethane (100 ml) was stirred at room temperature for 4 h. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml). The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (8.6 g, 87% of th.) was used in the next step without further purification. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml) The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a solution of 15 g (73.9 mmol) 5-bromo-2-fluorobenzaldehyde in diethyl ether (100 ml) at 0° C. were slowly added 27.1 ml (81.3 mmol) of ethyl magnesium bromide solution (3 M in diethyl ether). After stirring at 0° C. for 3 h, water (20 ml) was carefully added upon which a white precipitate formed. The solid was filtered off and washed with tert-butylmethyl ether. The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (16.1 g, 93% of th.) was used in the next step without further purification. at 0° C. formed The solid was filtered off washed with tert-butylmethyl ether The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: A mixture of 10 g (42.9 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanol (Example 3A), 8.75 g (85.8 mmol) neutral aluminium oxide and 18.5 g (85.8 mmol) pyridinium chlorochromate in dichloromethane (100 ml) was stirred at room temperature for 4 h. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml). The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (8.6 g, 87% of th.) was used in the next step without further purification. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml) The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a solution of 15 g (73.9 mmol) 5-bromo-2-fluorobenzaldehyde in diethyl ether (100 ml) at 0° C. were slowly added 27.1 ml (81.3 mmol) of ethyl magnesium bromide (3 M solution in diethyl ether). After stirring at 0° C. for 3 h, water (20 ml) was carefully added upon which a white precipitate formed. The solid was filtered off and washed with tert-butylmethyl ether. The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (16.1 g, 93% of th.) was used in the next step without further purification. at 0° C. formed The solid was filtered off washed with tert-butylmethyl ether The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: A mixture of 10 g (42.9 mmol) 1-(5-bromo-2-fluorophenyl)-1-propanol (Example 5A), 8.75 g (85.8 mmol) neutral aluminium oxide and 18.5 g (85.8 mmol) pyridinium chlorochromate in dichloromethane (100 ml) was stirred at room temperature for 4 h. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml). The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (8.6 g, 87% of th.) was used in the next step without further purification. The mixture was then filtered through silica gel (200 g, 0.06-0.2 mm) which was thoroughly washed with dichloromethane (1000 ml) The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

Procedure: To a solution of 15 g (73.9 mmol) 5-bromo-2-fluorobenzaldehyde in diethyl ether (100 ml) at 0° C. were slowly added 27.1 ml (81.3 mmol) of ethyl magnesium bromide solution (3 M in diethyl ether). After stirring at 0° C. for 3 h, water (20 ml) was carefully added upon which a white precipitate formed. The solid was filtered off and washed with tert-butylmethyl ether. The combined filtrates were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The crude title compound thus obtained (16.1 g, 93% of th.) was used in the next step without further purification. at 0° C. formed The solid was filtered off washed with tert-butylmethyl ether The combined filtrates were washed with brine dried over sodium sulfate concentrated under reduced pressure

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

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

Procedure: To 1-(5-bromo-2-fluorophenyl)propan-1-ol (12.1 g, 64.8 mmol) in CH2Cl2 (100 mL) was added pyridinium dichromate (73.2 g, 194 mmol) and powdered molecular sieves. The mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered through a pad of diatomaceous earth and washed with diethyl ether. The combined ether and CH2Cl2 layers were collected and concentrated under vacuum to afford 1-(5-bromo-2-fluorophenyl)propan-1-one (12.6 g, 98%) as a syrup. 1H NMR (CDCl3): δ 7.9-8.0 (m, 1H), 7.5-7.6 (m, 1H), 7.0 (t, 1H), 3.0-3.1 (m, 2H), 1.2 (t, 3H). The reaction mixture was filtered through a pad of diatomaceous earth washed with diethyl ether The combined ether and CH2Cl2 layers were collected concentrated under vacuum

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

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (10 g, 49 mmol) in diethyl ether (20 mL) at 15° C., was added drop wise at 15° C. EtMgBr (7.22 g, 54.2 mmol). The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with cold water and NH4Cl solution. It was extracted with diethyl ether and the ether layer was washed with saturated aqueous NaCl, dried over anhydrous Na2SO4 and concentrated under vacuum to afford 1-(5-bromo-2-fluorophenyl)propan-1-ol (12.1 g, 98%) as a syrup. 1H NMR (CDCl3): δ 7.6-7.7 (m, 1H), 7.2-7.3 (m, 1H), 6.9 (t, 1H), 4.9 (brs, 1H), 1.8 (m, 2H), 1.0 (t, 3H). The reaction mixture was quenched with cold water and NH4Cl solution It was extracted with diethyl ether the ether layer was washed with saturated aqueous NaCl dried over anhydrous Na2SO4 concentrated under vacuum