3-[diethoxymethyl(ethoxy)phosphoryl]propan-1-amine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.41 g of p-chlorobenzaldehyde are added to a solution of 2.53 g of 3-aminopropyl(diethoxymethyl)phosphinic acid ethyl ester in 10 ml of anhydrous methanol, and the resulting clear solution is stirred at room temperature for 30 minutes. There are then added first 0.6 g of glacial acetic acid and then, dropwised, 0.21 g of sodium cyanoborohydride in solution in 5 ml of methanol. An exothermic reaction begins. The mixture is stirred at 20° for 3 hours and adjusted at pH 8, and the solvent is removed. The residue is dissolved in dichlormethane and washed with water. The organic phase is separated off, dried over sodium sulfate and concentrated to dryness by evaporation. The oil that remains is purified by chomatography on silica gel, yielding 3-(p-chlorobenzylamino)propyl(diethoxymethyl)phosphinic acid ethyl ester in the form of a yellowish oil. An exothermic reaction The mixture is stirred at 20° for 3 hours the solvent is removed The residue is dissolved in dichlormethane washed with water The organic phase is separated off dried over sodium sulfate concentrated to dryness by evaporation The oil that remains is purified by chomatography on silica gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 98.5 mg (0.389 mmol) of ethyl 3-aminopropyl (diethoxymethyl)phosphinate (from Step B) and 84.9 mg (0.389 mmol) of 4-octylbenzaldehyde in 1 mL of MeOH at rt was treated with 12.2 mg (0.194 mmol) Na(CN)BH3. The resulting reaction mixture was stirred at rt for 16 hr. The reaction was quenched with 0.5 mL of 12 N HCl, then heated up to 80° C. for 1 hr. The mixture was cooled and concentrated. HPLC purification (LC-2) afforded 60 mg (47%) of the title compound: 1H NMR (500 MHz, CD3OD) δ 0.88 (t, J=7.1, 3H), 1.25-1.33 (m, 10H), 1.59-1.66 (m, 4H), 1.90-1.96 (m, 2H), 2.63 (t, J=7.7, 2H), 3.09 (t, J=6.9, 2H), 4.12 (s, 2H), 7.03 (d, J=505.6, 1H), 7.27 (d, J=8.0, 2H), 7.38 (d, J=8.0, 2H); LC-1: 3.02 min; ESI-MS 326 (M+H). The resulting reaction mixture The reaction was quenched with 0.5 mL of 12 N HCl heated up to 80° C. for 1 hr The mixture was cooled concentrated HPLC purification (LC-2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 98.5 mg (0.389 mmol) of ethyl 3-aminopropyl (diethoxymethyl)phosphinate (from Step B) and 84.9 mg (0.389 mmol) of 4-octylbenzaldehyde in 1 mL of MeOH at rt was treated with 12.2 mg (0.194 mmol) Na(CN)BH3. The resulting reaction mixture was stirred at rt for 16 hr. The reaction was quenched with 0.5 mL of 12 N HCl, then heated up to 80° C. for 1 hr. The mixture was cooled and concentrated. HPLC purification (LC-2) afforded 60 mg (47%) of the title compound: 1H NMR (500 MHz, CD3OD) δ 0.88 (t, J=7.1, 3H), 1.25-1.33 (m, 10H), 1.59-1.66 (m, 4H), 1.90-1.96 (m, 2H), 2.63 (t, J=7.7, 2H), 3.09 (t, J=6.9, 2H), 4.12 (s, 2H), 7.03 (d, J=505.6, 1H), 7.27 (d, J=8.0, 2H), 7.38 (d, J=8.0, 2H); LC-1: 3.02 min; ESI-MS 326 (M+H). The resulting reaction mixture The reaction was quenched with 0.5 mL of 12 N HCl heated up to 80° C. for 1 hr The mixture was cooled concentrated HPLC purification (LC-2)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2.47 g (9.91 mmol) of ethyl 2-cyanoethyl (diethoxymethyl)phosphinate (from Step A) in 20 mL 2.0 M ammonia in EtOH was added 250 mg Raney Nickel. The mixture was subjected to hydrogenation conditions (H2, 40 psi, rt) for 16 hr. The reaction mixture was filtered over Celite and partitioned between CH2Cl2 and H2O. The aqueous phase was extracted twice with CH2Cl2. The organic layer and extractions were combined, dried, and concentrated to provide 2.13 g (85% yield) of the title compound: 1H NMR (500 MHz) δ 1.23 (dt, J1=7.1, J2=1.6 6H), 1.29 (t, J=7.1, 3H), 1.42 (s, br, 2H), 1.71-1.82 (m, 4H), 2.72-2.75 (m, 2H), 3.63-3.70 (m, 2H), 3.78-3.86 (m, 2H), 4.08-4.21 (m, 2H), 4.64 (d, J=6.7, 1H); ESI-MS 254 (M+H). The reaction mixture was filtered over Celite partitioned between CH2Cl2 and H2O The aqueous phase was extracted twice with CH2Cl2 The organic layer and extractions dried concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.6 g of ethyl 2-cyanoethyl(diethoxymethyl)phosphinate in 450 ml of ethanol is added to 82 g of an 8% solution of ammonia in ethanol. To this is added 5 ml of Raney Nickel and the resulting mixture is hydrogenated at 1 bar until the theoretical amount of hydrogen has been taken up. The mixture is then filtered, the filtrate is concentrated under reduced pressure and the crude product is distilled to give ethyl 3-aminopropyl(diethoxymethyl)phosphinate, b.p. 150° C./0.01 mbar, 31P=+46.4 ppm (CDCl3). The mixture is then filtered the filtrate is concentrated under reduced pressure the crude product is distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.6 g of ethyl 2-cyanoethyl(diethoxymethyl)phosphinate in 450 ml of ethanol is added to 82 g of an 8% solution of ammonia in ethanol. To this is added 5 ml of Raney Nickel and the resulting mixture is hydrogenated at 1 bar until the theoretical amount of hydrogen has been taken up. The mixture is then filtered, the filtrate is concentrated under reduced pressure and the crude product is distilled to give ethyl 3-aminopropyl(diethoxymethyl)phosphinate, b.p. 150° C./0.01 mbar, 31P=+46.4 ppm (CDCl3). The mixture is then filtered the filtrate is concentrated under reduced pressure the crude product is distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.41 g of p-chlorobenzaldehyde are added to a solution of 2.53 g of 3-aminopropyl(diethoxymethyl)phosphinic acid ethyl ester in 10 ml of anhydrous methanol, and the resulting clear solution is stirred at room temperature for 30 minutes. There are then added first 0.6 g of glacial acetic acid and then, dropwise, 0.21 g of sodium cyanoborohydride in solution in 5 ml of methanol. An exothermic reaction begins. The mixture is stirred at 20° for 3 hours and adjusted to pH 8, and the solvent is removed. The residue is dissolved in dichloromethane and washed with water. The organic phase is separated off, dried over sodium sulfate and concentrated to dryness by evaporation. The oil that remains is purified by chromatography on silica gel, yielding 3-(p-chlorobenzylamino)propyl(diethoxymethyl)phosphinic acid ethyl ester in the form of a yellowish oil. An exothermic reaction The mixture is stirred at 20° for 3 hours the solvent is removed The residue is dissolved in dichloromethane washed with water The organic phase is separated off dried over sodium sulfate concentrated to dryness by evaporation The oil that remains is purified by chromatography on silica gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1.41 g of p-chlorobenzaldehyde are added to a solution of 2.53 g of 3-aminopropyl(diethoxymethyl)phosphinic acid ethyl ester in 10 ml of anhydrous methanol, and the resulting clear solution is stirred at room temperature for 30 minutes. There are then added first 0.6 g of glacial acetic acid and then, dropwise, 0.21 g of sodium cyanoborohydride in solution in 5 ml of methanol. An exothermic reaction begins. The mixture is stirred at 20° for 3 hours and adjusted to pH 8, and the solvent is removed. The residue is dissolved in dichloromethane and washed with water. The organic phase is separated off, dried over sodium sulfate and concentrated to dryness by evaporation. The oil that remains is purified by chromatography on silica gel, yielding 3-(p-chlorobenzylamino)propyl(diethoxymethyl)phosphinic acid ethyl ester in the form of a yellowish oil. An exothermic reaction The mixture is stirred at 20° for 3 hours the solvent is removed The residue is dissolved in dichloromethane washed with water The organic phase is separated off dried over sodium sulfate concentrated to dryness by evaporation The oil that remains is purified by chromatography on silica gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 9.6 g of ethyl 2-cyanoethyl(diethoxymethyl)phosphinate in 450 ml of ethanol is added to 82 g of an 8% solution of ammonia in ethanol. To this is added 5 ml of Raney Nickel and the resulting mixture is hydrogenated at 1 bar until the theoretical amount of hydrogen has been taken up. The mixture is then filtered, the filtrate is concentrated under reduced pressure and the crude product is distilled to give ethyl 3-aminopropyl(diethoxymethyl)phosphinate, b.p. 150° C./0.01 mbar, 31P=+46.4 ppm (CDCl3). The mixture is then filtered the filtrate is concentrated under reduced pressure the crude product is distilled

反応条件: temp:0.00; pressure:0.00; stir: