1-(bromomethyl)-4-chloro-2-fluorobenzene

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:

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: 361.5 g of 4-chloro-2-fluorotoluene, 520 g of chlorobenzene, 6 g of conc. H2SO4, 467 g of 47% strength hydrobromic acid and 2.7 g of 2,2'-azobis(2-methylpropionitrile) were mixed at 70° C. in a 4 l stirred apparatus. 620.5 g of a 10% strength aqueous hydrogen peroxide solution and a solution of 16.5 g of 2,2'-azobis(2-methylpropionitrile) in 270 g of chlorobenzene were simultaneously added dropwise over the course of 1.5 hours. The mixture was then stirred at 70° C. for 1 hour. GC analysis of the org. phase: The mixture was then stirred at 70° C. for 1 hour

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

Procedure: The title compound was prepared according to the process disclosed in Japanese Unexamined Patent Publication No. 106593/1986. The process was carried out as follows. A 5.0 g quantity of 2'-deoxy-5'-O-trityl-5-fluorouridine was dissolved in 40 ml of tetrahydrofuran. To the solution was added 856 mg of 60% sodium hydride, followed by 1 hour of stirring at room temperature. After addition of 2.58 g of 4-chloro-2-fluorobenzyl bromide, the mixture was stirred at room temperature for 2 hours. The reaction mixture was cooled to 0° C. and saturated ammonium chloride was added in excess. The tetrahydrofuran layer was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The solvent was distilled off at reduced pressure, and the residue was purified by silica gel column chromatography (eluate: n-hexane-ethyl acetate (3:2)), giving 5.03 g of the title compound (yield 78%). The title compound was prepared the mixture was stirred at room temperature for 2 hours The reaction mixture was cooled to 0° C. The tetrahydrofuran layer was washed with a saturated aqueous solution of sodium chloride dried over magnesium sulfate The solvent was distilled off at reduced pressure the residue was purified by silica gel column chromatography (eluate: n-hexane-ethyl acetate (3:2))

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: