4-diethoxyphosphorylaniline

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 mixture of 4-(4-chlorophenyl)-2-phenyl-5-oxazolepropionic acid (500 mg), triethylamine (230 mg) and tetrahydrofuran (10 ml) was added ethyl chlorocarbonate (250 mg) at −40° C., and the mixture was stirred for 1 hr. Diethyl 4-aminophenylphosphonate (420 mg) was added, and the mixture was stirred at room temperature for 5 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography and 3-[4-(4-chlorophenyl)-2-phenyl-5-oxazolyl]-N-[4-(diethylphosphono)phenyl]propionamide (295 mg, yield 36%) was obtained as colorless prism crystals from a fraction eluted with ethyl acetate-chloroform (1:1, volume ratio). melting point: 139–140° C. (recrystallized from dichloromethane-isopropyl ether). the mixture was stirred at room temperature for 5 hrs extracted with ethyl acetate The organic layer was washed with water dried over anhydrous magnesium sulfate concentrated The residue was purified by silica gel column chromatography

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

Procedure: Compound 2 was prepared in an analogous manner to that of Compound 1 using diethyl 4-aminophenylphosphonate (Intermediate 2.2) as the amine. 1H-NMR (300 MHz, CD3OD, ppm): 7.86 (d, 1H), 7.69 (m, 3H), 7.55 (m, 3H), 7.21 (m, 2H), 6.73 (s, 1H), 4.70 (m, 2H), 4.48 (d, 1H), 3.79 (m, 1H), 3.46 (m, 1H), 3.09 (s, 3H). MS (ES, m/z): 527 [M+H]+.

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

Procedure: Into a 50-mL round-bottom flask, was placed a solution of diethyl 4-nitrophenylphosphonate (1.07 g, 4.13 mmol, 1.00 equiv), TEA (3 mL), Palladium carbon (0.025 g). This was followed by the addition of formic acid (2 mL) dropwise with stirring at room temperature. The resulting solution was heated to reflux for 3 hr. The reaction was then quenched by the addition of 5 mL of water and the solids were filtered out. The resulting filtrate was extracted with 5×10 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate. This resulted in 800 mg (85%) of diethyl 4-aminophenylphosphonate as a white solid. Into a 50-mL round-bottom flask, was placed The resulting solution was heated to reflux for 3 hr The reaction was then quenched by the addition of 5 mL of water the solids were filtered out The resulting filtrate was extracted with 5×10 mL of dichloromethane dried over anhydrous sodium sulfate This resulted in 800 mg (85%) of diethyl 4-aminophenylphosphonate as a white solid

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

Procedure: Into a 50-mL round-bottom flask, was placed a solution of diethyl 4-nitrophenylphosphonate (1.07 g, 4.13 mmol, 1.00 equiv), TEA (3 mL), Palladium carbon (0.025 g). This was followed by the addition of formic acid (2 mL) dropwise with stirring at room temperature. The resulting solution was heated to reflux for 3 hr. The reaction was then quenched by the addition of 5 mL of water and the solids were filtered out. The resulting filtrate was extracted with 5×10 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate. This resulted in 800 mg (85%) of diethyl 4-aminophenylphosphonate as a white solid. Into a 50-mL round-bottom flask, was placed The resulting solution was heated to reflux for 3 hr The reaction was then quenched by the addition of 5 mL of water the solids were filtered out The resulting filtrate was extracted with 5×10 mL of dichloromethane dried over anhydrous sodium sulfate This resulted in 800 mg (85%) of diethyl 4-aminophenylphosphonate as a white solid

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

Procedure: A mixture of diethyl (4-nitrophenyl)phosphonate (150 mg, 0.58 mmol), EtOH (40 ml) and 10% Pd/C (30 mg) was hydrogenated under 50 psi of hydrogen pressure at 40° C. for 6 h. After cooling to room temperature, the reaction mixture was filtered and the filtrate concentrated in vacuo to afford 130 mg of desired diethyl (4-aminophenyl)phosphonate (yield: 98%), which was used directly in further chemistries without purification. the reaction mixture was filtered the filtrate concentrated in vacuo

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

Procedure: To a mixture of 4-(4-chlorophenyl)-2-phenyl-5-oxazolepropionic acid (500 mg), triethylamine (230 mg) and tetrahydrofuran (10 ml) was added ethyl chlorocarbonate (250 mg) at −40° C., and the mixture was stirred for 1 hr. Diethyl 4-aminophenylphosphonate (420 mg) was added, and the mixture was stirred at room temperature for 5 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography and 3-[4-(4-chlorophenyl)-2-phenyl-5-oxazolyl]-N-[4-(diethylphosphono)phenyl]propionamide (295 mg, yield 36%) was obtained as colorless prism crystals from a fraction eluted with ethyl acetate-chloroform (1:1, volume ratio). melting point: 139–140° C. (recrystallized from dichloromethane-isopropyl ether). the mixture was stirred at room temperature for 5 hrs extracted with ethyl acetate The organic layer was washed with water dried over anhydrous magnesium sulfate concentrated The residue was purified by silica gel column chromatography

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

Procedure: To a mixture of 4-(4-chlorophenyl)-2-phenyl-5-oxazolepropionic acid (500 mg), triethylamine (230 mg) and tetrahydrofuran (10 ml) was added ethyl chlorocarbonate (250 mg) at −40° C., and the mixture was stirred for 1 hr. Diethyl 4-aminophenylphosphonate (420 mg) was added, and the mixture was stirred at room temperature for 5 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography and 3-[4-(4-chlorophenyl)-2-phenyl-5-oxazolyl]-N-[4-(diethylphosphono)phenyl]propionamide (295 mg, yield 36%) was obtained as colorless prism crystals from a fraction eluted with ethyl acetate-chloroform (1:1, volume ratio). melting point: 139–140° C. (recrystallized from dichloromethane-isopropyl ether). the mixture was stirred at room temperature for 5 hrs extracted with ethyl acetate The organic layer was washed with water dried over anhydrous magnesium sulfate concentrated The residue was purified by silica gel column chromatography

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

Procedure: Compound 2 was prepared in an analogous manner to that of Compound 1 using diethyl 4-aminophenylphosphonate (Intermediate 2.2) as the amine. 1H-NMR (300 MHz, CD3OD, ppm): 7.86 (d, 1H), 7.69 (m, 3H), 7.55 (m, 3H), 7.21 (m, 2H), 6.73 (s, 1H), 4.70 (m, 2H), 4.48 (d, 1H), 3.79 (m, 1H), 3.46 (m, 1H), 3.09 (s, 3H). MS (ES, m/z): 527 [M+H]+.

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

Procedure: Into a 50-mL round-bottom flask, was placed a solution of diethyl 4-nitrophenylphosphonate (1.07 g, 4.13 mmol, 1.00 equiv), TEA (3 mL), Palladium carbon (0.025 g). This was followed by the addition of formic acid (2 mL) dropwise with stirring at room temperature. The resulting solution was heated to reflux for 3 hr. The reaction was then quenched by the addition of 5 mL of water and the solids were filtered out. The resulting filtrate was extracted with 5×10 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate. This resulted in 800 mg (85%) of diethyl 4-aminophenylphosphonate as a white solid. Into a 50-mL round-bottom flask, was placed The resulting solution was heated to reflux for 3 hr The reaction was then quenched by the addition of 5 mL of water the solids were filtered out The resulting filtrate was extracted with 5×10 mL of dichloromethane dried over anhydrous sodium sulfate This resulted in 800 mg (85%) of diethyl 4-aminophenylphosphonate as a white solid

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

Procedure: Compound 2 was prepared in an analogous manner to that of Compound 1 using diethyl 4-aminophenylphosphonate (Intermediate 2.2) as the amine. 1H-NMR (300 MHz, CD3OD, ppm): 7.86 (d, 1H), 7.69 (m, 3H), 7.55 (m, 3H), 7.21 (m, 2H), 6.73 (s, 1H), 4.70 (m, 2H), 4.48 (d, 1H), 3.79 (m, 1H), 3.46 (m, 1H), 3.09 (s, 3H). MS (ES, m/z): 527 [M+H]+.