2,5-Difluorobenzyl alcohol

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: To a solution of (2,5-difluoro-phenyl)-methanol (4.8 g, 33.6 mmol) in dichloromethane (40 mL) was added drop wise phosphorus tribromide (94 g, 33.6 mmol). The mixture was stirred at room temperature for 16 h. The reaction was poured onto ice/water. The aqueous phase was made basic with sodium bicarbonate. The aqueous phase was extracted with dichloromethane. The organic phase was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10) to give the title compound (3.5 g, 50%). The reaction was poured onto ice/water The aqueous phase was extracted with dichloromethane The organic phase was concentrated under reduced pressure The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10)

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

Procedure: To a solution of (2,5-difluoro-phenyl)-methanol (4.8 g, 33.6 mmol) in dichloromethane (40 mL) was added drop wise phosphorus tribromide (94 g, 33.6 mmol). The mixture was stirred at room temperature for 16 h. The reaction was poured onto ice/water. The aqueous phase was made basic with sodium bicarbonate. The aqueous phase was extracted with dichloromethane. The organic phase was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10) to give the title compound (3.5 g, 50%). The reaction was poured onto ice/water The aqueous phase was extracted with dichloromethane The organic phase was concentrated under reduced pressure The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10)

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

Procedure: To a solution of (2,5-difluoro-phenyl)-methanol (4.8 g, 33.6 mmol) in dichloromethane (40 mL) was added drop wise phosphorus tribromide (94 g, 33.6 mmol). The mixture was stirred at room temperature for 16 h. The reaction was poured onto ice/water. The aqueous phase was made basic with sodium bicarbonate. The aqueous phase was extracted with dichloromethane. The organic phase was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10) to give the title compound (3.5 g, 50%). The reaction was poured onto ice/water The aqueous phase was extracted with dichloromethane The organic phase was concentrated under reduced pressure The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10)

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

Procedure: To a solution of (2,5-difluoro-phenyl)-methanol (4.8 g, 33.6 mmol) in dichloromethane (40 mL) was added drop wise phosphorus tribromide (94 g, 33.6 mmol). The mixture was stirred at room temperature for 16 h. The reaction was poured onto ice/water. The aqueous phase was made basic with sodium bicarbonate. The aqueous phase was extracted with dichloromethane. The organic phase was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10) to give the title compound (3.5 g, 50%). The reaction was poured onto ice/water The aqueous phase was extracted with dichloromethane The organic phase was concentrated under reduced pressure The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10)

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

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

Procedure: The title compound was prepared by a procedure similar to that described for E9 starting from (2,5-difluorophenyl)methanol and 7-chloro-1,2,2-trimethyl-2,3-dihydroimidazo[1,2-c]pyrimidin-5(1H)-one.

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

Procedure: At 0° C., 4-chlorobenzenethiol (5.45 g, 38.2 mmol), triphenylphosphine (11.1 g, 41.6 mmol) and diisopropyl azodicarboxylate (8.16 ml, 41.6 mmol) were sequentially added to a tetrahydrofuran (150 ml) solution of 2,5-difluorobenzyl alcohol (5.00 g, 34.7 mmol). The reaction mixture was stirred at room temperature for 4 days, followed by concentration. The residue thus obtained was purified by silica gel column chromatography (1% ethyl acetate-hexane) to give 2-[(4-chlorophenyl)thiomethyl]-1,4-difluorobenzene (2.68 g, 29%) as a colorless oil. followed by concentration The residue thus obtained was purified by silica gel column chromatography (1% ethyl acetate-hexane)

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

Procedure: 2,5-Difluorobenzyl cis-2,6-dimethylpiperazine-1-carboxylate hydrochloride was prepared from cis 1-chlorocarbonyl-2,6-dimethyl-4-tert-butoxycarbonylpiperazine and 2,5-difluorobenzyl alcohol according to the methods described for Examples 52 and 54 to give the product as a white solid (0.247 g, 77% overall); (Found: C, 52.5; H, 6.1; N, 8.7%. C14H18F2N2O2.HCl requires C, 52.4; H, 6.0; N, 8.7%); δH (400 MHz, DMSO-d6), 9.98 (2H, br),7.29 (3H, m), 5.15 (2H, s), 4.31 (2H, m), 3.15 (2H, d, J 12.8 Hz), 3.06 (2H, dd, J 5 and 13 Hz), and 1.31 (6H, d, J 7.2 Hz).

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

Procedure: Starting with 4-(2,4-difluorophenyl)-N-{3-[(methylsulfonyl)methyl]phenyl}-1,3,5-triazin-2-amine (70 mg; 0.184 mmol), intermediate 42.1, and 2,5-difluorobenzyl alcohol (107 mg; 0.736 mmol), example 81 was prepared analogously to the procedure for the preparation of example 42. was prepared analogously to the procedure for the preparation of example 42