methyl 2-(4-chlorophenyl)-2-oxoacetate

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

Procedure: A solution of 29.9 g (0.15 mol) of the keto ester of Example 2 in 300 ml of acetonitrile were treated with 117.9 g of PPh3 (0.45 mol), and 69.3 g (0.45 mol) of carbon tetrachloride were then added dropwise. After the reaction solution had remained at approximately 56° C. for 4 hours, it was concentrated; the residue obtained was chromatographed over silica gel with cyclohexane/MtBE (3:1). This gave 39.2 g of the title compound. were then added dropwise it was concentrated the residue obtained was chromatographed over silica gel with cyclohexane/MtBE (3:1)

Conditions: temp:22.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 97.2 g of a 75% strength aqueous N-methylmorpholine N-oxide solution were added with ice-cooling to a solution of 100 g (0.38 mol) of the compound of Example 1 in 400 ml of dimethyl sulfoxide (DMSO). After the mixture had been stirred for 24 hours at 20 to 25° C., it was poured into water and extracted with methyl tert-butyl ether (MtBE). After the organic phases had been dried, stripped from the solvent and chromatographed on silica gel (cyclohexane/MtBE [3:1]), 69 g of the title compound was obtained. extracted with methyl tert-butyl ether (MtBE) After the organic phases had been dried chromatographed on silica gel (cyclohexane/MtBE [3:1])

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

Procedure: Selenium dioxide (35.5 g; 320 mmol) was dissolved in 250 mL of MeOH (warm to reflux with stirring), and 19.6 g (315 mmol) of α-bromo-4-chloroacetophenone was added. The reaction mixture was warmed to reflux for 24 hours, cooled, filtered and concentrated leaving an orange oil. The oil was diluted with 1500 mL of Et2O and washed three times with 200 mL of H2O and once with 200 mL of brine, dried (Na2SO4) and concentrated. The crude oil was crystallized from Et2O and hexanes at -20° C. The white needles were filtered while cold and washed with small portions of cold hexanes to yield 22 g (35%) of methyl p-chlorophenyl-α-oxoacetate, The reaction mixture was warmed to reflux for 24 hours cooled filtered concentrated leaving an orange oil washed three times with 200 mL of H2O once with 200 mL of brine, dried (Na2SO4) concentrated The crude oil was crystallized from Et2O and hexanes at -20° C The white needles were filtered while cold and washed with small portions of cold hexanes

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

Procedure: Selenium dioxide (35.5 g; 320 mmol) was dissolved in 250 mL of MeOH (warm to reflux with stirring), and 19.6 g (315 mmol) of α-bromo-4-chloroacetophenone was added. The reaction mixture was warmed to reflux for 24 hours, cooled, filtered and concentrated leaving an orange oil. The oil was diluted with 1500 mL of Et2O and washed three times with 200 mL of H2O and once with 200 mL of brine, dried (Na2SO4) and concentrated. The crude oil was crystallized from Et2O and hexanes at -20° C. The white needles were filtered while cold and washed with small portions of cold hexanes to yield 22 g (35%) of methyl p-chlorophenyl-α-oxoacetate, m.p. 56°-57° C., 1H-NMR (CDCl3)δ8.0-7.9 (m, 2H), 7.5-7.4 (m, 2H), 3.9 (s, 3H); 13C-NMR (CDCl3)δ184.4, 163.5, 141.6, 131.4, 131.0, 129.3, 52.7. The reaction mixture was warmed to reflux for 24 hours cooled filtered concentrated leaving an orange oil washed three times with 200 mL of H2O once with 200 mL of brine, dried (Na2SO4) concentrated The crude oil was crystallized from Et2O and hexanes at -20° C The white needles were filtered while cold and washed with small portions of cold hexanes