triethyl phosphate

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: Two g (7 mmol) 6-chloropurine riboside (available from Sigma Chemical Co., St. Louis, Mo.) was stirred with 17 ml triethylphosphate and was reacted with phosphoryl chloride in the presence of water as described in Chem. Scrip. 19: 165-70(1972). After hydrolysis of the phosphodichloridate, 9.5 ml ethylenediamine (140 mmol) was added and allowed to react at room temperature for 3 hr. The reaction mixture was diluted to 4 liters with water and adjusted to pH 12 with sodium hydroxide. This solution was passed through a 5×30 cm column of Dowex 1×8 (available from Bio-Rad Laboratories, Richmond, Calif.) in the acetate form. Then the column was washed with 3 liters 0.01M ammonium chloride and the chromatogram was developed with a linear gradient generated with 3 liters water and 3 liters 1M acetic acid. An isolated peak of uv absorbing material eluted between 1800 ml and 2050 ml of the gradient was concentrated to about 25 ml under vacuum. While this solution stood at 7° C. overnight, white crystals formed and these were collected and dried to give 65 percent yield of the product. A sample was recrystallized from hot water for analysis. Calculated for C12H19N6O7P.2H2O: C, 33.8; H, 5.45; N, 19.7. Found: C, 34.3; H, 5.22; N, 19.7. Separate thin-layer chromatograms developed with two solvent systems, the first consisting of 4 parts 0.5M ammonium acetate to 1 part ethanol and the second consisting of 3 parts isobutyric acid to 5 parts 1M ammonium hydroxide, each showed one component which quenched fluorescence and reacted with ninhydrin. The compound in 0.1N hydrochloric acid had an absorption maximum at 264 nm and the millimolar extinction coefficient was 17.7 which spectral properties are characteristic of N6 -alkylated adenosine derivatives. was added to react at room temperature for 3 hr Then the column was washed with 3 liters 0.01M ammonium chloride An isolated peak of uv absorbing material eluted between 1800 ml and 2050 ml of the gradient was concentrated to about 25 ml under vacuum white crystals formed these were collected dried

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 4-(bromomethyl)benzoate (25 g, 109 mmol) and triethyl phosphate (24.3 ml, 142 mmol) was stirred at 150° C. for 24 h. The resulting mixture was purified by distillation (165-172° C., 1 mmHg) to obtain diethyl 4-(methoxycarbonyl)benzylphosphonate (21.5 g, 69%). To a mixture of diethyl 4-(methoxycarbonyl)benzylphosphonate (20.5 g, 71.5 mmol), 15-crown-5 (1.4 ml, 7.1 mmol) and THF (120 ml) was added sodium hydride (60% in oil, 2.9 g, 71.5 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 h. A solution of tert-butyl 4-oxo-1-piperidinecarboxylate (11.9 g, 59.6 mmol) in THF (45 ml) was added dropwise to the resulting mixture over period of 10 min at 0° C. The mixture was stirred at room temperature for 20 h. The resulting mixture was poured into ice-water (200 ml) and the whole was extracted with ethyl acetate (100 ml×2). The extracts were washed with 5% aqueous sodium bicarbonate(100 ml), saturated sodium chloride solution (100 ml) successively. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel 200 g, ethyl acetate/hexane=1/10) followed by recrystallization from hexane to give tert-butyl 4-(4-methoxycarbonylbenzylidene)piperidine-1-carboxylate (6.9 g, 35%) as a colorless crystalline powder. A mixture of tert-butyl 4-(4-methoxycarbonylbenzylidene)piperidine-1-carboxylate (6 g, 18 mmol) in methanol (150 ml) was hydrogenated over 10% palladium carbon (50% wet, 1 g) for 5 h at room temperature. The catalyst was removed by filtration and the filtrate was concentrated in vacuo. The residue was purified by flash column chromatography (silica gel 90 g, ethyl acetate/hexane=1/10) to obtain the title compound (6.1 g, 100%) as pale yellow oil. The resulting mixture was purified by distillation (165-172° C., 1 mmHg)

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

Procedure: 2-(2-O-Acetyl-β-D-ribofuranosyl)selenazole-4-carboxamide is treated with 1 to 5 equivalents of phosphoryl chloride in the presence of triethylphosphate at 0 degrees C. After complete dissolution is obtained, the solution is poured over crushed ice and adjusted with sodium hydroxide solution to pH 7, extracted with chloroform, and placed on a column of ion exchange resin (Dowex AG 1X8, formate). The column is first washed with water, then the product is eluted with a gradient of water-formic acid. The fractions containing pure product are pooled and evaporated to dryness. The residue is recrystallized from ethanol-water to provide the free acid of the title compound as a crystalline solid. After complete dissolution is obtained the solution is poured over crushed ice extracted with chloroform The column is first washed with water the product is eluted with a gradient of water-formic acid The fractions containing pure product evaporated to dryness The residue is recrystallized from ethanol-water

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 114 mg (0.194 mmole) of (3S, 4R)-3-[(R)-1-t-butyldimethylsilyloxyethyl]-1-(p-nitrobenzyloxyethyl)-4-[(phenylthio)carbonylmethyl]-2-azetidinone, 258 mg (1.55 mmole) of triethyl phosphate and 10 ml of toluene was stirred at 100° C. for 18 hours under a nitrogen atmosphere. The solvent was distilled off, and the residue was purified by the procedure described in Example 5, to give 95 mg (yield 88%) of the title product , in the form of crystals. The solvent was distilled off the residue was purified by the procedure

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The reaction was carried out under argon. Triethyl phosphate (1.049 g, 5.76 mmol) and diphosphorus pentoxide (0.454 g) were stirred at 40° C. overnight. The mixture was then diluted with MTBE (25 ml), and 4-formyl-3-[(1-methylethyl)sulfonyl]benzonitrile (0.759 g, 3.2 mmol), 1-[3-(tri-fluoromethyl)phenyl]urea (0.653 g, 3.2 mmol) and allyl acetoacetate (0.682 g, 4.8 mmol; 1.5 eq.) were added. The mixture was stirred under reflux for 6 h. The reaction mixture was then concentrated by distillative removal of MTBE and subsequently heated at 90° C. for a further 2 h. For work-up, residual solvent was removed under reduced pressure and the residue was suspended in MTBE (20 ml) and then filtered off with suction. The solid was washed with MTBE (2×10 ml). This gave 1.25 g (48% of theory) of the title compound. were added under reflux for 6 h The reaction mixture was then concentrated by distillative removal of MTBE For work-up, residual solvent was removed under reduced pressure filtered off with suction The solid was washed with MTBE (2×10 ml)