1-[ethoxy(methylsulfanylmethyl)phosphoryl]oxyethane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30.7 ml of n-butyl lithium (1.63 M, n-hexane solution) was diluted with 35 ml of THF, and the diluted solution was cooled to −78° C. in an atmosphere of argon. Thereto was added a solution of 10.4 g of diethyl methylthiomethylphosphonate in 10 ml of THF, followed by stirring at −78° C. for 1 hour. Thereto was added dropwise a solution of 5 g of 5-n-butyl-7-chloropyrazolo[1,5-a]pyrimidine in 5 ml of THF, followed by stirring at −78° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed sequentially with aqueous ammonium chloride solution, water and saturated saline and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane=1:3→1:1). As a result, 5.9 g of diethyl (5-n-butylpyrazolo[1,5-a]pyrimidin-7-yl)methylthiomethylphosphonate was obtained as an oily product. by stirring at −78° C. for 1 hour washed sequentially with aqueous ammonium chloride solution, water and saturated saline concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane=1:3→1:1)

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

Procedure: To a mixture of 3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazole-4-carbaldehyde (2.0 g), diethyl (methylthio)methylphosphonate (0.89 g) and N,N-dimethylformamide (50 mL) was added sodium hydride (60% in oil, 0.20 g) at room temperature and the mixture was stirred at room temperature for 15 hrs. The reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:2, v/v) to give colorless crystals. To a mixture of the obtained crystal and tetrahydrofuran (50 mL) was added m-chloroperbenzoic acid (0.66 g) at room temperature, and the mixture was stirred at the same temperature for 2 hrs. Saturated sodium sulfite aqueous solution was added to the reaction mixture, and the mixture was stirred at room temperature for 10 min, and extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-methanol (100:1, v/v) to give 2-(2-furyl)-4-({2-methoxy-4-[({4-[(E)-2-(methylsulfinyl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]phenoxy}methyl)-5-methyl-1,3-oxazole as colorless crystals (0.81 g, yield 36%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 156-157° C. the mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate concentrated eluted with ethyl acetate-hexane (1:2 v/v) to give colorless crystals the mixture was stirred at the same temperature for 2 hrs the mixture was stirred at room temperature for 10 min extracted with ethyl acetate The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine dried over anhydrous magnesium sulfate concentrated eluted with ethyl acetate-methanol (100:1

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

Procedure: To a mixture of 3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-phenyl-1H-pyrazole-4-carbaldehyde (2.0 g), diethyl (methylthio)methylphosphonate (0.89 g) and N,N-dimethylformamide (50 mL) was added sodium hydride (60% in oil, 0.20 g) at room temperature and the mixture was stirred at room temperature for 15 hrs. The reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:2, v/v) to give colorless crystals. To a mixture of the obtained crystal and tetrahydrofuran (50 mL) was added m-chloroperbenzoic acid (0.66 g) at room temperature, and the mixture was stirred at the same temperature for 2 hrs. Saturated sodium sulfite aqueous solution was added to the reaction mixture, and the mixture was stirred at room temperature for 10 min, and extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-methanol (100:1, v/v) to give 2-(2-furyl)-4-({2-methoxy-4-[({4-[(E)-2-(methylsulfinyl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]phenoxy}methyl)-5-methyl-1,3-oxazole as colorless crystals (0.81 g, yield 36%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 156-157° C. the mixture was extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous magnesium sulfate concentrated eluted with ethyl acetate-hexane (1:2 v/v) to give colorless crystals the mixture was stirred at the same temperature for 2 hrs the mixture was stirred at room temperature for 10 min extracted with ethyl acetate The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate and saturated brine dried over anhydrous magnesium sulfate concentrated eluted with ethyl acetate-methanol (100:1

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

Procedure: Oxydation of diethyl methylthiomethylphosphonate include anodic oxidation in NaOMe/MeOH (saturated with CO2) to give the O, S-acetal of diethoxyphosphinylformaldehyde, which upon oxidation may give the corresponding sulfone as Diethyl methoxy(methylsulfone)phenyl phosphonate (Shankaran, K et al. 2001).

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

Procedure: Oxydation of diethyl methylthiomethylphosphonate include anodic oxidation in NaOMe/MeOH (saturated with CO2) to give the O, S-acetal of diethoxyphosphinylformaldehyde, which upon oxidation may give the corresponding sulfone as Diethyl methoxy(methylsulfone)phenyl phosphonate (Shankaran, K et al. 2001).

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 30.7 ml of n-butyl lithium (1.63 M, n-hexane solution) was diluted with 35 ml of THF, and the diluted solution was cooled to −78° C. in an atmosphere of argon. Thereto was added a solution of 10.4 g of diethyl methylthiomethylphosphonate in 10 ml of THF, followed by stirring at −78° C. for 1 hour. Thereto was added dropwise a solution of 5 g of 5-n-butyl-7-chloropyrazolo[1,5-a]pyrimidine in 5 ml of THF, followed by stirring at −78° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed sequentially with aqueous ammonium chloride solution, water and saturated saline and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane=1:3→1:1). As a result, 5.9 g of diethyl (5-n-butylpyrazolo[1,5-a]pyrimidin-7-yl)methylthiomethylphosphonate was obtained as an oily product. by stirring at −78° C. for 1 hour washed sequentially with aqueous ammonium chloride solution, water and saturated saline concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane=1:3→1:1)