(2-三氟甲基苄基)膦酸二乙酯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a cooled solution of KHMDS (0.5M in toluene, 50 ml, 25 mmol) at 0° C. in dry tetrahydrofuran (70 ml) under nitrogen is added freshly prepared neat (2-trifluoromethyl-benzyl)-phosphonic acid diethyl ester (5.7 ml, 25 mmol, 1 equiv.). The reaction is warmed to room temperature over 1 hour and then racemic (4-benzyl-morpholin-2-yl)-phenyl-methanone (7 g, 25 mmol in 25 ml of dry tetrahydrofuran) is added dropwise. The reaction is left at room temperature and stirred for 2 hours. At the end of this time the reaction solvent is removed under reduced vacuum and replaced with diethyl ether prior to quenching with water. After extraction with diethyl ether and drying (MgSO4) the solvent is again removed under reduced pressure. The resulting residue is purified by column chromatography on silica gel to yield a colourless oil (6.5 g, 61%). The reaction is left at room temperature At the end of this time the reaction solvent is removed under reduced vacuum to quenching with water After extraction with diethyl ether drying (MgSO4) the solvent is again removed under reduced pressure The resulting residue is purified by column chromatography on silica gel

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium iodide (3.85 g, 25.6 mmol, 1 equiv.) in acetonitrile at room temperature under argon is added neat 1-chloromethyl-2-trifluoromethyl-benzene (commercially available from Acros Organics USA). To the resulting milky suspension is added freshly distilled triethyl phosphite (4.26 g, 25.6 mmol, 1 equiv.) and the resulting solution is stirred overnight at room temperature. After that time further triethyl phosphite (2.13 g, 12.9 mmol, 0.5 equiv.) is added and the reaction mixture heated at reflux for 1 hour. After cooling down to room temperature all volatiles were evaporated under reduced pressure. The residue is taken-up in dichloromethane and filtered through paper and the filtrate is concentrated under reduced pressure to yield the desired material as a clear oil pure enough to be used in the following step without further purification (7.46 g, 98%). the reaction mixture heated at reflux for 1 hour After cooling down to room temperature all volatiles were evaporated under reduced pressure filtered through paper the filtrate is concentrated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium iodide (3.85 g, 25.6 mmol, 1 equiv.) in acetonitrile at room temperature under argon is added neat 1-chloromethyl-2-trifluoromethyl-benzene (commercially available from Acros Organics USA). To the resulting milky suspension is added freshly distilled triethyl phosphite (4.26 g, 25.6 mmol, 1 equiv.) and the resulting solution is stirred overnight at room temperature. After that time further triethyl phosphite (2.13 g, 12.9 mmol, 0.5 equiv.) is added and the reaction mixture heated at reflux for 1 hour. After cooling down to room temperature all volatiles were evaporated under reduced pressure. The residue is taken-up in dichloromethane and filtered through paper and the filtrate is concentrated under reduced pressure to yield the desired material as a clear oil pure enough to be used in the following step without further purification (7.46 g, 98%). the reaction mixture heated at reflux for 1 hour After cooling down to room temperature all volatiles were evaporated under reduced pressure filtered through paper the filtrate is concentrated under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The diethyl 2-trifluoromethylbenzylphosphonate (1.22 g, 4.12 mmol) was dissolved in a mixture of 50 mL of conc hydrochloric acid and 5 mL of EtOH and was heated at reflux temperature for 17 hours. After cooling the mixture in an ice bath, white crystalline acid was collected to give 0.46 g, 46% of the desired product, mp=190°-192° C.; D.C.I.M.S. [MH+, 241]. was heated at reflux temperature for 17 hours After cooling the mixture in an ice bath white crystalline acid was collected

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-trifluoromethylbenzyl chloride (2.0 g, 10.0 mmol) and triethyl phosphite (2.13 g, 13 mmol) was heated at 160° C. under nitrogen for 3 hours. The excess triethyl phosphite was removed by distillation and the crude product obtained was distilled at 87°-90° C. (0.05 mm Hg) and isolated as a colorless oil; yield, 1.68 g, 56.8%; D.C.I.M.S.[MH+, 297]. The excess triethyl phosphite was removed by distillation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The diethyl 2-trifluoromethylbenzylphosphonate (1.22 g, 4.12 mmol) was dissolved in a mixture of 50 mL of conc hydrochloric acid and 5 mL of EtOH and was heated at reflux temperature for 17 hours. After cooling the mixture in an ice bath, white crystalline acid was collected to give 0.46 g, 46% of the desired product, mp=190°-192° C.; D.C.I.M.S. [MH+, 241]. was heated at reflux temperature for 17 hours After cooling the mixture in an ice bath white crystalline acid was collected

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-trifluoromethylbenzyl chloride (2.0 g, 10.0 mmol) and triethyl phosphite (2.13 g, 13 mmol) was heated at 160° C. under nitrogen for 3 hours. The excess triethyl phosphite was removed by distillation and the crude product obtained was distilled at 87°-90° C. (0.05 mm Hg) and isolated as a colorless oil; yield, 1.68 g, 56.8%; D.C.I.M.S.[MH+,297]. The excess triethyl phosphite was removed by distillation

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a cooled solution of KHMDS (0.5M in toluene, 50 ml, 25 mmol) at 0° C. in dry tetrahydrofuran (70 ml) under nitrogen is added freshly prepared neat (2-trifluoromethyl-benzyl)-phosphonic acid diethyl ester (5.7 ml, 25 mmol, 1 equiv.). The reaction is warmed to room temperature over 1 hour and then racemic (4-benzyl-morpholin-2-yl)-phenyl-methanone (7 g, 25 mmol in 25 ml of dry tetrahydrofuran) is added dropwise. The reaction is left at room temperature and stirred for 2 hours. At the end of this time the reaction solvent is removed under reduced vacuum and replaced with diethyl ether prior to quenching with water. After extraction with diethyl ether and drying (MgSO4) the solvent is again removed under reduced pressure. The resulting residue is purified by column chromatography on silica gel to yield a colourless oil (6.5 g, 61%). The reaction is left at room temperature At the end of this time the reaction solvent is removed under reduced vacuum to quenching with water After extraction with diethyl ether drying (MgSO4) the solvent is again removed under reduced pressure The resulting residue is purified by column chromatography on silica gel

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium iodide (3.85 g, 25.6 mmol, 1 equiv.) in acetonitrile at room temperature under argon is added neat 1-chloromethyl-2-trifluoromethyl-benzene (commercially available from Acros Organics USA). To the resulting milky suspension is added freshly distilled triethyl phosphite (4.26 g, 25.6 mmol, 1 equiv.) and the resulting solution is stirred overnight at room temperature. After that time further triethyl phosphite (2.13 g, 12.9 mmol, 0.5 equiv.) is added and the reaction mixture heated at reflux for 1 hour. After cooling down to room temperature all volatiles were evaporated under reduced pressure. The residue is taken-up in dichloromethane and filtered through paper and the filtrate is concentrated under reduced pressure to yield the desired material as a clear oil pure enough to be used in the following step without further purification (7.46 g, 98%). the reaction mixture heated at reflux for 1 hour After cooling down to room temperature all volatiles were evaporated under reduced pressure filtered through paper the filtrate is concentrated under reduced pressure