dichlorophosphoryloxymethane

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: Anhydrous pyridine (5 mL) was put in a reactor containing a small magnetic stirbar and cooled in an ice bath. Methyldichlorophosphate (1.0 mL) was added dropwise. The mixture was kept cold for another 15 minutes during which a precipitate of N-methylpyridinium dichlorophosphate formed. Adamantane ethanol dissolved in 5 mL of pyridine was added to the reactor and the reactor sealed after the reaction mixture was frozen. The resulting mixture was stirred overnight at room temperature. The sealed reacted was then opened and the resulting mixture was poured into 10% sodium bicarbonate (50 mL). This resulting solution was then evaporated in vacuo. 800 mL of water was added to the remaining solid and product extracted with 150 mL ether. The aqueous phase was acidified with 2 N HCl to pH=1.4 and then extracted with 3×150 mL of CHCl3:nBuOH (7:3). The organic layer was washed with water and the mixed solvents were evaporated in vacuo to form a solid phase. This solid was recrystallized with acetone/hexane, affording a white solid with 27% yield. Electrospray mass spectroscopy analysis revealed the pure, desired product. containing a small magnetic stirbar cooled in an ice bath

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

Procedure: 5-(tert-Butyldiphenylsilanyloxy)-3-(4-trifluoromethylphenyl)pentanoic acid amide (640 mg) was dissolved in methylene chloride (13 mL), and 1,8-diazabicyclo[5,4,0]undec-7-ene (862 μL) and methyl dichlorophosphate (301 μL) were added at 0° C. After stirring at room temperature for 1.5 hours, the reaction was terminated with a saturated sodium bicarbonate aqueous solution. The organic layer was washed with brine and then dried over magnesium sulfate. Concentration under reduced pressure gave an oil. The oil was allowed to pass through a silica gel pad (mobile phase:ethyl acetate:heptane=1:2) to obtain the title compound (600 mg). the reaction was terminated with a saturated sodium bicarbonate aqueous solution The organic layer was washed with brine dried over magnesium sulfate Concentration under reduced pressure gave an oil

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

Procedure: Methyl dichlorophosphate (1.9 mL) was added dropwise at 20° C. or less to an ice-cooled solution of 5-chloro-2-(4-chloro-2-trifluoromethylphenyl)pentanoic acid amide (3.0 g) and 1,8-diazabicyclo[5,4,0]undec-7-ene (6.4 mL) in methylene chloride (30 mL). After completion of the dropwise addition, the reaction solution was stirred at room temperature for one hour and 25 minutes. A saturated sodium bicarbonate aqueous solution was added to the reaction solution. After stirring for five minutes, the organic layer was separated. The aqueous layer was reextracted with methylene chloride. The combined organic layers were sequentially washed with 1 N hydrochloric acid, water, a saturated sodium bicarbonate aqueous solution and brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent:heptane:ethyl acetate=49:1→19:1) to obtain 2.25 g of the title compound. After completion of the dropwise addition After stirring for five minutes the organic layer was separated The combined organic layers were sequentially washed with 1 N hydrochloric acid, water a saturated sodium bicarbonate aqueous solution and brine, dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent:heptane:ethyl acetate=49:1→19:1)

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

Conditions: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1.418 g of pyrocatechol were added 1.917 g of methyl dichlorophosphate and 11 ml of acetonitrile. The mixture was cooled to -25° C. and 2.605 g of triethylamine was added dropwise at -25° C. to -20° C. with stirring. The dropping funnel was washed with 1 ml of acetonitrile and the washings were added to the mixture. After stirring at the same temperature for 10 minutes, the reaction mixture was allowed to return to 10° C. and then filtered. The filtration residue was washed with a 5-ml and 3-ml portion of acetonitrile. The filtrate and washings were concentrated under reduced pressure on a water bath at 15° C. to 20° C. to give 3.102 g of methyl o-phenylene phosphate as a slightly turbid oil. The dropping funnel was washed with 1 ml of acetonitrile the washings were added to the mixture After stirring at the same temperature for 10 minutes to return to 10° C. filtered The filtration residue was washed with a 5-ml and 3-ml portion of acetonitrile The filtrate and washings were concentrated under reduced pressure on a water bath at 15° C. to 20° C.

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

Procedure: 3,4-Dihydroxytoluene (1.686 g, 13.58 mM) was dissolved in 40 ml of ether and, using 2.748 g of triethylamine and 2.022 g of methyl dichlorophosphate, the reaction mixture was treated in the same manner as in Reference Example 5. There was obtained 2,400 g (88.4% yield) of 2-methoxy-5-methyl-2-oxo-1,3,2-benzodioxaphosphole as a viscous oil. the reaction mixture was treated in the same manner as in Reference Example 5

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

Procedure: Triethylamine (2.211 g, 21.86 mM) was added to a solution of1.989 g (10.93 mM) of ethyl 3,4-dihydroxybenzoate in 30 ml of ether. The mixture was cooled to -30° C. to -20° C. and a solution of 1.627 g (10.93 mM) of methyl dichlorophosphate in 10 ml of ether was added thereto dropwise with stirring over 10 minutes. The reaction mixture was stirred at the same temperature for 5 minutes, the bath was then removed and the temperature was allowed to rise to 20° C. Filtration and washing were carried out by the procedure of Reference Example 1, and the filtrate and washings were concentrated at room temperature (20°~25° C.) under reduced pressure. There was obtained 2.387 g (84.6% yield) of 5-ethoxycarbonyl-2-methoxy-2-oxo-1,3,2-benzo-dioxaphosphole as a viscous oil. The mixture was cooled to -30° C. to -20° C. The reaction mixture was stirred at the same temperature for 5 minutes the bath was then removed to rise to 20° C Filtration washing the filtrate and washings were concentrated at room temperature (20°~25° C.) under reduced pressure

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

Procedure: Anhydrous pyridine (10 mL, Aldrich, Milwaukee, Wis.) was cooled in an ice bath and methyl dichlorophosphate (1.488 g, 10 mmol, Aldrich, Milwaukee, Wis.) was added dropwise. The mixture was kept cold for a further 15 min. During this period a precipitate of N-methylpyridinium dichlorophosphate formed. 1-Adamantane ethanol (4.758 g, 26.4 mmol, Aldrich, Milwaukee, Wis.) was added, and the sealed mixture was stirred overnight at room temperature. It was then poured into 10% NaHCO3 solution (50 mL) and the pyridine was evaporated under vacuum. The slightly yellow solid was dissolved in 1 L of water and extracted with ether (three 150 mL portions). The aqueous phase was acidified with 2 N HCl to pH 1, and then extracted with three 150 mL portions of CHCl3:n-BuOH (7:3). The combined organic layer (ether and CHCl3:n-BuOH) was washed with water and a slightly yellow precipitate was formed in the mixed solvents, at which point the solvents were evaporated under vacuum. A slightly yellow solid was formed and was recrystallized from acetone/hexane. The solid was dried under vacuum, yield 60%.

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

Procedure: Anhydrous pyridine (10 mL, Aldrich, Milwaukee, Wis.) was cooled in an ice bath and methyl dichlorophosphate (1.488 g, 10 mmol, Aldrich, Milwaukee, Wis.) was added dropwise. The mixture was kept cold for a further 15 min. During this period a precipitate of N-methylpyridinium dichlorophosphate formed. 1-Adamantane ethanol (4.758 g, 26.4 mmol, Aldrich, Milwaukee, Wis.) was added, and the sealed mixture was stirred overnight at room temperature. It was then poured into 10% NaHCO3 solution (50 mL) and the pyridine was evaporated under vacuum. The slightly yellow solid was dissolved in 1 L of water and extracted with ether (three 150 mL portions). The aqueous phase was acidified with 2 N HCl to pH 1, and then extracted with three 150 mL portions of CHCl3:n-BuOH (7:3). The combined organic layer (ether and CHCl3:n-BuOH) was washed with water and a slightly yellow precipitate was formed in the mixed solvents, at which point the solvents were evaporated under vacuum. A slightly yellow solid was formed and was recrystallized from acetone/hexane. The solid was dried under vacuum, yield 60%.