methyl 4-(chloromethyl)benzoate

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:

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

Procedure: To a solution of p-methoxycarbonylbenzyl alcohol (332.0 g, 2.0 mol) in methylene chloride (600 mL) is added thionyl chloride (380 g, 3.2 mol) dropwise over 3 hours and the reaction mixture heated at gentle reflux for 6 hours, allowing excess gases to escape. The excess thionyl chloride and methylene chloride are removed and the yellow oil triturated with hexane to yield a total of 300 g (81.5% yield) of white, solid methyl α-chloro-p-toluate, the identity of which is confirmed by elemental analysis and mass spectrum analysis as follows: the reaction mixture heated at gentle reflux for 6 hours The excess thionyl chloride and methylene chloride are removed the yellow oil triturated with hexane

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

Procedure: To a solution of 2-hydroxy-3-nitro-5-trifluoromethylpyridine (1.0 g) in toluene (10 ml), methyl 4-chloromethylbenzoate (1.32 g) and silver oxide (1.23 g) were added in a stream of argon. The mixture was refluxed for 18 hours with heating. The reaction mixture was filtered. The filtrate was concentrated. The residue was recrystallized from ethyl acetate to give the title compound (982 mg) having the following physical data. The mixture was refluxed for 18 hours with heating The reaction mixture was filtered The filtrate was concentrated The residue was recrystallized from ethyl acetate

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

Procedure: To a solution of 2-hydroxy-3-nitro-5-trifluoromethylpyridine (1.0 g) in toluene (10 ml), methyl 4-chloromethylbenzoate (1.32 g) and silver oxide (1.23 g) were added in a stream of argon. The mixture was refluxed for 18 hours with heating. The reaction mixture was filtered. The filtrate was concentrated. The residue was recrystallized from ethyl acetate to give the title compound (982 mg) having the following physical data. The mixture was refluxed for 18 hours with heating The reaction mixture was filtered The filtrate was concentrated The residue was recrystallized from ethyl acetate

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

Procedure: At 0° C. and under argon, 343.4 mg (0.64 mmol) of 2-(benzyloxy)benzyl-triphenylphosphonium bromide from Ex. III are suspended in 20 ml of THF, and 0.48 ml of butyllithium (0.76 mmol, 1.6 M solution in hexane) is added. The deep-orange solution is stirred at 0° C. for 30 min, and a solution of 195 mg (0.64 mmol) of methyl 6-formyl-7-(4-methoxycarbonylphenyl)heptanoate (prepared analogously to Example I from t-butyl 2-oxocyclohexanecarboxylate and methyl 4-chloromethylbenzoate, cf. EP-A-0 341 551) in 15 ml of THF is added dropwise at this temperature. The mixture is stirred at 0° C. for 30 min. At 0° C., water is added, and the mixture is then warmed to room temperature and extracted with ethyl acetate. The organic phase is washed with sodium chloride solution, dried with magnesium sulfate and concentrated using a rotary evaporator. For purification, the substance was chromatographed on 40 g of silica gel 60 (particle size 0.040-0.063 mm) using the mobile phase petroleum ether/ether 4:1 to 1:1. At 0° C. The mixture is stirred at 0° C. for 30 min the mixture is then warmed to room temperature extracted with ethyl acetate The organic phase is washed with sodium chloride solution dried with magnesium sulfate concentrated a rotary evaporator For purification the substance was chromatographed on 40 g of silica gel 60 (particle size 0.040-0.063 mm)

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

Procedure: In a 4-necked flask, equipped with stirrer, reflux cooler, thermometer and drip funnel, a solution of 110.8 g (0.6 mole) of p-chloromethylbenzoic acid methyl ester in 150 ml of hexamethylphosphoric triamide is added dropwise, with stirring, at 25° C to a solution (prepared at 5°-10° C) of 38.4 g (0.3 mole) of 2,2-dimethylimidazolidine-4,5-dione and 32.4 g (0.6 mole) of sodium methylate in 225 ml of anhydrous methanol and 225 ml of hexamethylphosphoric triamide. In a 4-necked flask, equipped with stirrer reflux cooler