六乙基亚磷酸胺

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask equipped with a dry ice condenser was flame dried under a nitrogen sream, and charged with 5.0 g (20 mmol) of chlorotri-n-butylsilane and 10 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 6.2 mL (66 mmol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cooling bath was removed and the mixture was allowed to warm to the temperature of the refluxing Freon (-59°C.). To this cold solution was added, dropwise, 8.0 mL (29 mmol) of hexaethylphosphorous triamide. The resulting solution was stirred at reflux for 1 hour. Removal of the condenser and continued stirring for 1 hour resulted in evaporation of excess Freon and warming of the solution to room temperature. Dilution with 30 mL of dichloromethane, water (three 30 mL portions) and 1N HCl (two 30 mL portions) washing, drying (MgSO4), and concentration afforded a residue which was short path distilled to give 3.6 g (64% yield) of tri-n-butyltrifluoromethylsilane: bp 53°-58° C. at 0.5 torr; 1H NMR (CDCl3) δ 0.60-1.10 (m, 5H), 1.10-1.56 (m, 4H); 19F NMR (CDCl3, relative to CFCl3) -61.6 ppm (s); IR (neat) 2956, 2925, 2872, 1214, 1058 cm-1 ; mass spectrum (70 eV) m/z (relative intensity) 199 (30, M-CF3), 143 (80), 105 (30), 101 (27), 87 (30), 77 (66), 63 (43), 59 (41), 55 (54), 47 (25), 43 (20), 41 (100). Anal. Calcd. for C13H27F3Si: C, 58.16; H, 10.14. Found: C, 58.26; H, 10.09. A flask equipped with a dry ice condenser was flame dried under a nitrogen sream condensed into a graduated tube was warmed to room temperature to distill into the flask The cooling bath was removed to warm to the temperature of the refluxing Freon (-59°C.) To this cold solution was added at reflux for 1 hour Removal of the condenser continued stirring for 1 hour resulted in evaporation of excess Freon warming of the solution to room temperature Dilution with 30 mL of dichloromethane, water (three 30 mL portions) and 1N HCl (two 30 mL portions) washing drying (MgSO4), and concentration afforded a residue which distilled

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask equipped with a dry ice condenser was flame dried under a nitrogen stream, and charged with 25 g (0.17 mol) of chlorotriethylsilane and 40 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 40 mL (0.43 mol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cold solution was treated dropwise with 66mL (0.24 mol) of hexaethylphosphorous triamide, allowed to stir at -78° C. for two hours, and allowed to stir at room temperature overnight. Low boiling components were then short path distilled into a cold (-78° C.) receiving flask at >1 torr with the pot temperature kept at <50° C. The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation to give 22.0 g of 98% pure (69% yield) triethyltrifluoromethylsilane: bp 52°-54° C. at 10 torr; 1H NMR (CDCl3) δ 0.59-1.16 (m); 19F NMR (CDCl3, relative to CFCl3) - 61.3 ppm (s); IR (neat) 2960, 2915, 2882, 1458, 1413, 1206, 1055, 1020, 734, 693 cm-1 ; mass spectrum (70 eV) m/z (relative intensity) 115 (66, M-CF3), 105 (46), 87 (85), 77 (100), 59 (56), 49 (41), 47 (37), 41 (38). Anal. Calcd. for C7H15F3Si: C, 45.62; H, 8.20. Found: C, 47.53; H, 8.56. A flask equipped with a dry ice condenser was flame dried under a nitrogen stream condensed into a graduated tube was warmed to room temperature to distill into the flask to stir at room temperature overnight short path distilled into a cold (-78° C.) kept at <50° C The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask equipped with a dry ice condenser was flame dried under a nitrogen sream, and charged with 5.0g (20 mmol) of chloro -tri-n-butylsilane and 10 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 6.2 mL (66 mmol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cooling bath was removed and the mixture was allowed to warm to the temperature of the refluxing Freon (-59° C.). To this cold solution was added, dropwise, 8.0 mL (29 mmol) of hexaethylphosphorous triamide. The resulting solution was stirred at reflux for 1 hour. Removal of the condenser and continued stirring for 1 hour resulted in evaporation of excess Freon and warming of the solution to room temperature. Dilution with 30 mL of dichloromethane, water (three 30 mL portions) and lN HCl (two 30 mL portions) washing, drying (MgSO4), and concentration afforded a residue which was short path distilled to give 3.6g (64% yield) of tri-n-butyltrifluoromethylsilane: bp 53-58° C. at 0.5 torr; 1H NMR (CDCl3) δ 0.60-1.10 (m, 5H), 1.10-1.56 (m, 4H); 19F NMR (CDCl3, relative to CFCl3) -61.6 ppm (s); IR (neat) 2956, 2925, 2872, 1214, 1058 cm-1; mass spectrum (70 eV) m/z (relatiVe intensity) 199 (30, M-CF3), 143 (80), 105 (30), 101 (27), 87 (30), 77 (66), 63 (43), 59 (41), 55 (54), 47 (25), 43 (20), 41 (100). Anal. Calcd. for C13H27F3Si: C, 58.16; H, 10.14. Found: C, 58.26; H, 10.09. A flask equipped with a dry ice condenser was flame dried under a nitrogen sream condensed into a graduated tube was warmed to room temperature to distill into the flask The cooling bath was removed to warm to the temperature of the refluxing Freon (-59° C.) To this cold solution was added at reflux for 1 hour Removal of the condenser continued stirring for 1 hour resulted in evaporation of excess Freon warming of the solution to room temperature Dilution with 30 mL of dichloromethane, water (three 30 mL portions) and lN HCl (two 30 mL portions) washing drying (MgSO4), and concentration afforded a residue which distilled

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask equipped with a dry ice condenser was flame dried under a nitrogen sream, and charged with 5.0g (20 mmol) of chloro -tri-n-butylsilane and 10 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 6.2 mL (66 mmol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cooling bath was removed and the mixture was allowed to warm to the temperature of the refluxing Freon (-59° C.). To this cold solution was added, dropwise, 8.0 mL (29 mmol) of hexaethylphosphorous triamide. The resulting solution was stirred at reflux for 1 hour. Removal of the condenser and continued stirring for 1 hour resulted in evaporation of excess Freon and warming of the solution to room temperature. Dilution with 30 mL of dichloromethane, water (three 30 mL portions) and lN HCl (two 30 mL portions) washing, drying (MgSO4), and concentration afforded a residue which was short path distilled to give 3.6g (64% yield) of tri-n-butyltrifluoromethylsilane: bp 53-58° C. at 0.5 torr; 1H NMR (CDCl3) δ 0.60-1.10 (m, 5H), 1.10-1.56 (m, 4H); 19F NMR (CDCl3, relative to CFCl3) -61.6 ppm (s); IR (neat) 2956, 2925, 2872, 1214, 1058 cm-1; mass spectrum (70 eV) m/z (relatiVe intensity) 199 (30, M-CF3), 143 (80), 105 (30), 101 (27), 87 (30), 77 (66), 63 (43), 59 (41), 55 (54), 47 (25), 43 (20), 41 (100). Anal. Calcd. for C13H27F3Si: C, 58.16; H, 10.14. Found: C, 58.26; H, 10.09. A flask equipped with a dry ice condenser was flame dried under a nitrogen sream condensed into a graduated tube was warmed to room temperature to distill into the flask The cooling bath was removed to warm to the temperature of the refluxing Freon (-59° C.) To this cold solution was added at reflux for 1 hour Removal of the condenser continued stirring for 1 hour resulted in evaporation of excess Freon warming of the solution to room temperature Dilution with 30 mL of dichloromethane, water (three 30 mL portions) and lN HCl (two 30 mL portions) washing drying (MgSO4), and concentration afforded a residue which distilled

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask equipped with a dry ice condenser was flame dried under a nitrogen stream, and charged with 25g (0.17 mol) of chlorotriethylsilane and 40 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 40 mL (0.43 mol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cold solution was treated dropwise with 66mL (0.24 mol) of hexaethylphosphorous triamide, allowed to stir at -78° C. for two hours, and allowed to stir at room temperature overnight. Low boiling components were then short path distilled into a cold (-78° C.) receiving flask at>1 torr with the pot temperature kept at<50° C. The distillate was further fractionated by removal of the dichloromethane (40-45° C. at atmospheric pressure) and short path distillation to give 22.0 g of 98% pure (69% yield) triethyltrifluoromethylsilane: bp 52-54° C. at 10 torr; 1H NMR (CDCl3) δ 0.59-1.16 (m); 19F NMR (CDCl3, relative to CFCl3) -61.3 ppm (s); IR (neat) 2960, 2915, 2882, 1458, 1413, 1206, 1055, 1020, 734, 693 cm-1; mass spectrum (70 eV) m/z (relative intensity) 115 (66, M-CF3), 105 (46), 87 (85), 77 (100), 59 (56), 49 (41), 47 (37), 41 (38). Anal. Calcd. for C7H15F3Si: C, 45.62; H, 8.20. Found: C, 47.53; H, 8.56. A flask equipped with a dry ice condenser was flame dried under a nitrogen stream condensed into a graduated tube was warmed to room temperature to distill into the flask to stir at room temperature overnight short path distilled into a cold (-78° C.) kept at<50° C The distillate was further fractionated by removal of the dichloromethane (40-45° C. at atmospheric pressure) and short path distillation

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask equipped with a dry ice condenser was flame dried under a nitrogen stream, and charged with 3.1 mL (17 mmol) of chlorodiphenylphosphine and 10 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 4 mL (43 mmol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cold solution was treated dropwise with 7 mL (26 mmol) of hexaethylphosphorous triamide, allowed to stir at "78° C. for 1 hour, and allowed to stir at room temperature overnight. Dilution with 50 mL of dichloromethane, water washing (three 50 mL portions), drying (MgSO4), and concentration afforded a brown liquid which was purified by flash chromatography on 50g of silica gel (230-400 mesh) eluted with petroleum ether to give 2.9g (68% yield) of diphenyltrifluoromethylphosphine as a colorless liquid. 19F NMR (CDCl3, relative to CFCl3) -55.60 ppm (d, JPF =73 Hz); 31P NMR (CDCl3, relative to H3PO4) 3.11 ppm (quartet of pentets, JPF =73 Hz, JPH =8 Hz); mass spectrum (70 eV) m/z (relative intensity) 254 (41, M+), 185 (74), 183 (100), 127 (23), 107 (40), 77 (26), 69 (65), 51 (54). A flask equipped with a dry ice condenser was flame dried under a nitrogen stream condensed into a graduated tube was warmed to room temperature to distill into the flask to stir at room temperature overnight Dilution with 50 mL of dichloromethane, water washing (three 50 mL portions), drying (MgSO4), and concentration afforded a brown liquid which was purified by flash chromatography on 50g of silica gel (230-400 mesh) eluted with petroleum ether

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dibromodifluoromethane (16.2 g) and THF (30 ml) were put into a vessel under a nitrogen atmosphere and cooled to 10° C. Trisdiethylaminophosphine (38.2 g) in THF (50.0 ml) solution was added dropwise thereto and the stirring was continued for another 60 minutes. The compound (T-8) (16.5 g) in THF (400 ml) solution was then added dropwise in the temperature range of 20° C. to 35° C., and allowed to react overnight while the reaction mixture was coming to room temperature. The reaction mixture obtained was poured into ice-water (400 ml) and mixed. Organic and aqueous layers were separated by adding toluene (300 ml) and the aqueous layer was extracted with toluene. The organic layers combined were washed sequentially with water, 3N-hydrochloric acid and water, and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure and purified by means of column chromatography (silica gel; heptane/ethyl acetate), giving 4-[2-fluoro-4-(4′-pentyl-1,1′-bicyclohexane-4-yl)phenyl]difluoromethylenecyclohexane (T-9) (15.1 g). The yield based on the compound (T-8) was 85%. to react overnight while the reaction mixture was coming to room temperature The reaction mixture obtained mixed Organic and aqueous layers were separated by adding toluene (300 ml) the aqueous layer was extracted with toluene The organic layers combined were washed sequentially with water, 3N-hydrochloric acid and water dried over anhydrous magnesium sulfate The solution was concentrated under reduced pressure purified by means of column chromatography (silica gel; heptane/ethyl acetate)

反应条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dibromodifluoromethane (16.2 g) and THF (30 ml) were put into a vessel under a nitrogen atmosphere and cooled to 10° C. Trisdiethylaminophosphine (38.2 g) in THF (50.0 ml) solution was added dropwise thereto and the stirring was continued for another 60 minutes. The compound (T-8) (16.5 g) in THF (400 ml) solution was then added dropwise in the temperature range of 20° C. to 35° C., and allowed to react overnight while the reaction mixture was coming to room temperature. The reaction mixture obtained was poured into ice-water (400 ml) and mixed. Organic and aqueous layers were separated by adding toluene (300 ml) and the aqueous layer was extracted with toluene. The organic layers combined were washed sequentially with water, 3N-hydrochloric acid and water, and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure and purified by means of column chromatography (silica gel; heptane/ethyl acetate), giving 4-[2-fluoro-4-(4′-pentyl-1,1′-bicyclohexane-4-yl)phenyl]difluoromethylenecyclohexane (T-9) (15.1 g). The yield based on the compound (T-8) was 85%. to react overnight while the reaction mixture was coming to room temperature The reaction mixture obtained mixed Organic and aqueous layers were separated by adding toluene (300 ml) the aqueous layer was extracted with toluene The organic layers combined were washed sequentially with water, 3N-hydrochloric acid and water dried over anhydrous magnesium sulfate The solution was concentrated under reduced pressure purified by means of column chromatography (silica gel; heptane/ethyl acetate)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask equipped with a dry ice condenser was flame dried under a nitrogen sream, and charged with 5.0 g (20 mmol) of chlorotri-n-butylsilane and 10 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 6.2 mL (66 mmol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cooling bath was removed and the mixture was allowed to warm to the temperature of the refluxing Freon (-59°C.). To this cold solution was added, dropwise, 8.0 mL (29 mmol) of hexaethylphosphorous triamide. The resulting solution was stirred at reflux for 1 hour. Removal of the condenser and continued stirring for 1 hour resulted in evaporation of excess Freon and warming of the solution to room temperature. Dilution with 30 mL of dichloromethane, water (three 30 mL portions) and 1N HCl (two 30 mL portions) washing, drying (MgSO4), and concentration afforded a residue which was short path distilled to give 3.6 g (64% yield) of tri-n-butyltrifluoromethylsilane: bp 53°-58° C. at 0.5 torr; 1H NMR (CDCl3) δ 0.60-1.10 (m, 5H), 1.10-1.56 (m, 4H); 19F NMR (CDCl3, relative to CFCl3) -61.6 ppm (s); IR (neat) 2956, 2925, 2872, 1214, 1058 cm-1 ; mass spectrum (70 eV) m/z (relative intensity) 199 (30, M-CF3), 143 (80), 105 (30), 101 (27), 87 (30), 77 (66), 63 (43), 59 (41), 55 (54), 47 (25), 43 (20), 41 (100). Anal. Calcd. for C13H27F3Si: C, 58.16; H, 10.14. Found: C, 58.26; H, 10.09. A flask equipped with a dry ice condenser was flame dried under a nitrogen sream condensed into a graduated tube was warmed to room temperature to distill into the flask The cooling bath was removed to warm to the temperature of the refluxing Freon (-59°C.) To this cold solution was added at reflux for 1 hour Removal of the condenser continued stirring for 1 hour resulted in evaporation of excess Freon warming of the solution to room temperature Dilution with 30 mL of dichloromethane, water (three 30 mL portions) and 1N HCl (two 30 mL portions) washing drying (MgSO4), and concentration afforded a residue which distilled

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask equipped with a dry ice condenser was flame dried under a nitrogen stream, and charged with 25 g (0.17 mol) of chlorotriethylsilane and 40 mL of dichloromethane. After cooling the resulting solution to -78° C. and charging the condenser with dry ice and acetone, 40 mL (0.43 mol) of bromotrifluoromethane (Freon 13B1) that had been condensed into a graduated tube was warmed to room temperature and allowed to distill into the flask. The cold solution was treated dropwise with 66mL (0.24 mol) of hexaethylphosphorous triamide, allowed to stir at -78° C. for two hours, and allowed to stir at room temperature overnight. Low boiling components were then short path distilled into a cold (-78° C.) receiving flask at >1 torr with the pot temperature kept at <50° C. The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation to give 22.0 g of 98% pure (69% yield) triethyltrifluoromethylsilane: bp 52°-54° C. at 10 torr; 1H NMR (CDCl3) δ 0.59-1.16 (m); 19F NMR (CDCl3, relative to CFCl3) - 61.3 ppm (s); IR (neat) 2960, 2915, 2882, 1458, 1413, 1206, 1055, 1020, 734, 693 cm-1 ; mass spectrum (70 eV) m/z (relative intensity) 115 (66, M-CF3), 105 (46), 87 (85), 77 (100), 59 (56), 49 (41), 47 (37), 41 (38). Anal. Calcd. for C7H15F3Si: C, 45.62; H, 8.20. Found: C, 47.53; H, 8.56. A flask equipped with a dry ice condenser was flame dried under a nitrogen stream condensed into a graduated tube was warmed to room temperature to distill into the flask to stir at room temperature overnight short path distilled into a cold (-78° C.) kept at <50° C The distillate was further fractionated by removal of the dichloromethane (40°-45° C. at atmospheric pressure) and short path distillation

实验步骤: 投料: 取24 g上一步产物（68 mmol，1.0 eq）置于1 L三口瓶中，加入甲苯（340 mL，0.2 M），置换氮气三次，加入六乙基亚磷酸胺（15.14 g，16.8 mL，0.9 eq，ρ=0.903 g/mL），室温反应，体系呈白色浑浊，平行投入两个批次\n监测: 其中一个反应已变为凝胶状，取样用正己烷洗涤，抽滤，固体送HNMR（DMSO）：153228-2-5-S1，原料产物比例为2:1 20 min后第二个反应也变为凝胶状，取样相同处理后测HNMR：153228-2-5-S1-2，原料产物比例为2:1 各补加150 mL甲苯，换成大号搅拌子可继续搅动，保持氮气氛围冰箱过夜保存 10-21 继续反应 11:39 混合取样处理HNMR：153228-2-5-mix-S2，原料产物比例为0.68:1 14:35 混合取样处理HNMR：153228-2-5-mix-S3，原料产物比例为1:3 16:00 混合取样处理HNMR：153228-2-5-mix-S4，比例不变，停止反应 \n后处理: 正己烷稀释（1 L），抽滤，正己烷（1 L）洗涤滤饼，所得白色固体油泵拉溶残，得45 g，HNMR（DMSO）：C4X-153228-2-5-P，杂峰较少

实验步骤: 投料: 取上一步产物（70 mg，0.2 mmol）置于20 mL透明样品瓶中，置换氮气三次，加入甲苯（1 mL，0.2 M）和0.05 mL六乙基亚磷酸胺（45 mg，0.18 mmol），室温反应，体系呈白色浑浊\n监测: LCMS（DCM）：153228-2-2，原料和产物极性相近，难以分开，原料未反应完 12:15 LCMS：153228-2-2-2h，体系变为胶状，反应完全\n后处理: 加入正己烷3 mL，体系呈白色悬浊，抽滤，滤饼送LCMS（DCM）、HNMR（DMSO）：：C4X-153228-2，存在产物正信号，核磁主峰为产物，存在少量原料