N-乙基甲磺酰胺

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-ethyl-methanesulfonamide (Mijs et al. J. Chem. Soc. Chem. Com. 1972 p412) (5 g 40.6 mmol) was added to a suspension of sodium hydride (1.9 g, 55% in mineral oil) in anhydrous DMF (100 mL) under nitrogen. The mixture was warmed to 55° C. for one hour and 2,4-difluoronitrobenzene (4.4 mL) was added dropwise. The reaction was stirred at 60° C. overnight, poured into water (500 mL) and the product extracted into CH2Cl2 (5×100 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give an oily product. The remaining DMF was removed by trituration with petrol. The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1) to yield the desired product which was recrystallised from ethanol. Yield 3.5 g (33%). Calculated N % 10.68 C % 41.22 S % 12.23 H % 4.23; Found N % 10.68 C % 41.39 S % 12.22 H % 4.17. the product extracted into CH2Cl2 (5×100 mL) The organic extracts were washed with water dried over MgSO4 evaporated to give an oily product The remaining DMF was removed by trituration with petrol The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1)

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-ethyl-methanesulfonamide (Mijs et al. J. Chem. Soc. Chem. Com. 1972 p412) (5 g 40.6 mmol) was added to a suspension of sodium hydride (1.9 g, 55% in mineral oil) in anhydrous DMF (100 mL) under nitrogen. The mixture was warmed to 55° C. for one hour and 2,4-difluoronitrobenzene (4.4 mL) was added dropwise. The reaction was stirred at 60° C. overnight, poured into water (500 mL) and the product extracted into CH2Cl2 (5×100 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give an oily product. The remaining DMF was removed by trituration with petrol. The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1) to yield the desired product which was recrystallised from ethanol. Yield 3.5 g (33%). Calculated N, % 10.68; C, % 41.22; S, % 12.23; H, % 4.23. Found N, % 10.68; C, % 41.39; S, % 12.22; H, % 4.17. the product extracted into CH2Cl2 (5×100 mL) The organic extracts were washed with water dried over MgSO4 evaporated to give an oily product The remaining DMF was removed by trituration with petrol The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1)

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-ethyl-methanesulfonamide (Mijs et al. J. Chem. Soc. Chem. Com. 1972 p412) (5 g 40.6 mmol) was added to a suspension of sodium hydride (1.9 g, 55% in mineral oil) in anhydrous DMF (100 mL) under nitrogen. The mixture was warmed to 55° C. for one hour and 2,4-difluoronitrobenzene (4.4 mL) was added dropwise. The reaction was stirred at 60° C. overnight, poured into water (500 mL) and the product extracted into CH2Cl2 (5×100 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give an oily product. The remaining DMF was removed by trituration with petrol. The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1) to yield the desired product which was recrystallised from ethanol. Yield 3.5 g (33%). Calculated N, % 10.68; C, % 41.22; S, % 12.23; H, % 4.23. Found N, % 10.68; C, % 41.39; S, % 12.22; H, % 4.17. the product extracted into CH2Cl2 (5×100 mL) The organic extracts were washed with water dried over MgSO4 evaporated to give an oily product The remaining DMF was removed by trituration with petrol The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Triethylamine (0.043 ml, 0.1 equiv) was added to a mixture of N-ethylmethanesulfonamide (413 mg, 1.1 equiv) and 2-benzyloxymethyloxirane (500 mg, 3.04 mmol) prepared according to (J. Am. Chem. Soc., 1996, 118, 7094-7100) in anhydrous dioxane (1 ml). The reaction mixture was then heated to 50° C. overnight. As the reaction was not complete, it was heated to 100° C. for another 5 hours (reaction complete according to TLC). The volatiles were then removed in vacuo. Flash chromatography eluting with cyclohexane/Ethyl acetate (6/4 then 1/1) afforded 836 mg (2.91 mmol, 96%). LCMS (Method E) 1.44 min, M+H 288. 1H-NMR (CDCl3, 400 MHz): 7.43-7.27 (m, 5H), 4.57 (s, 2H), 4.11-3.90 (m, 1H), 3.62-3.44 (m, 2H), 3.43-3.20 (m, 4H), 2.90 (s, 3H), 1.14-1.33 (m, 3H). prepared it was heated to 100° C. for another 5 hours (reaction complete according to TLC) The volatiles were then removed in vacuo Flash chromatography eluting with cyclohexane/Ethyl acetate (6/4 1/1) afforded 836 mg (2.91 mmol, 96%) LCMS (Method E) 1.44 min, M+H 288

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Triethylamine (0.043 ml, 0.1 equiv) was added to a mixture of N-ethylmethanesulfonamide (413 mg, 1.1 equiv) and 2-benzyloxymethyloxirane (500 mg, 3.04 mmol) prepared according to (J. Am. Chem. Soc., 1996, 118, 7094-7100) in anhydrous dioxane (1 ml). The reaction mixture was then heated to 50° C. overnight. As the reaction was not complete, it was heated to 100° C. for another 5 hours (reaction complete according to TLC). The volatiles were then removed in vacuo. Flash chromatography eluting with cyclohexane/Ethyl acetate (6/4 then 1/1) afforded 836 mg (2.91 mmol, 96%). LCMS (Method E) 1.44 min, M+H 288. 1H-NMR (CDCl3, 400 MHz): 7.43-7.27 (m, 5H), 4.57 (s, 2H), 4.11-3.90 (m, 1H), 3.62-3.44 (m, 2H), 3.43-3.20 (m, 4H), 2.90 (s, 3H), 1.14-1.33 (m, 3H). prepared it was heated to 100° C. for another 5 hours (reaction complete according to TLC) The volatiles were then removed in vacuo Flash chromatography eluting with cyclohexane/Ethyl acetate (6/4 1/1) afforded 836 mg (2.91 mmol, 96%) LCMS (Method E) 1.44 min, M+H 288

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

实验步骤: A solution of 2.6 g of sulphur dichloride in 15 ml of dry diethyl ether was added over 10 minutes to a stirred solution of 3.1 g of N-ethylmethanesulphonamide in 15 ml of the same solvent, keeping the temperature between 10°-15° by means of external cooling. A solution of 2.0 g of dry pyridine in 15 ml of dry diethyl ether was then added over 15 minutes at the same temperature and the reaction mixture was allowed to warm to room temperature over 1 hour. The resulting suspension was added over 5 minutes to a solution of 7.2 g of 4-[2-chloro-4-(trifluoromethyl)phenoxy]aniline (1A) in 75 ml of dry diethyl ether containing 2.0 g of pyridine, keeping the temperature of the mixture between 5°-10° C. After stirring at 10°-15° for 1 hour, the reaction mixture was washed three times with water, the ether layer was separated, dried (MgSO4), and the solvent was evaporated under reduced pressure. The residue was purified by chromatography on silica gel using diethyl ether as eluent, to give 2, as a buff solid m.p.: 98°-101° C. between 10°-15° between 5°-10° C the reaction mixture was washed three times with water the ether layer was separated dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by chromatography on silica gel to give 2

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-ethyl-methanesulfonamide (Mijs et al. J. Chem. Soc. Chem. Com. 1972 p412) (5 g 40.6 mmol) was added to a suspension of sodium hydride (1.9 g, 55% in mineral oil) in anhydrous DMF (100 mL) under nitrogen. The mixture was warmed to 55° C. for one hour and 2,4-difluoronitrobenzene (4.4 mL) was added dropwise. The reaction was stirred at 60° C. overnight, poured into water (500 mL) and the product extracted into CH2Cl2 (5×100 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give an oily product. The remaining DMF was removed by trituration with petrol. The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1) to yield the desired product which was recrystallised from ethanol. Yield 3.5 g (33%). Calculated N % 10.68 C % 41.22 S % 12.23 H % 4.23; Found N % 10.68 C % 41.39 S % 12.22 H % 4.17. the product extracted into CH2Cl2 (5×100 mL) The organic extracts were washed with water dried over MgSO4 evaporated to give an oily product The remaining DMF was removed by trituration with petrol The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1)

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-ethyl-methanesulfonamide (Mijs et al. J. Chem. Soc. Chem. Com. 1972 p 412) (5 g 40.6 mmol) was added to a suspension of sodium hydride (1.9 g, 55% in mineral oil) in anhydrous DMF (100 mL) under nitrogen. The mixture was warmed to 55° C. for one hour and 2,4-difluoronitrobenzene (4.4 mL) was added dropwise. The reaction was stirred at 60° C. overnight, poured into water (500 mL) and the product extracted into CH2Cl2 (5×100 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give an oily product. The remaining DMF was removed by trituration with petrol. The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1) to yield the desired product which was recrystallised from ethanol. Yield 3.5 g (33%). Calculated N % 10,68 C % 41,22 S % 12,23H % 4,23; Found N % 10,68 C % 41,39 S % 12,22H % 4,17. the product extracted into CH2Cl2 (5×100 mL) The organic extracts were washed with water dried over MgSO4 evaporated to give an oily product The remaining DMF was removed by trituration with petrol The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1)

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-ethyl-methanesulfonamide (Mijs et al. J. Chem. Soc. Chem. Com. 1972 p 412) (5 g 40.6 mmol) was added to a suspension of sodium hydride (1.9 g, 55% in mineral oil) in anhydrous DMF (100 mL) under nitrogen. The mixture was warmed to 55° C. for one hour and 2,4-difluoronitrobenzene (4.4 mL) was added dropwise. The reaction was stirred at 60° C. overnight, poured into water (500 mL) and the product extracted into CH2Cl2 (5×100 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give an oily product. The remaining DMF was removed by trituration with petrol. The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1) to yield the desired product which was recrystallised from ethanol. Yield 3.5 g (33%). Calculated N % 10,68 C % 41,22 S % 12,23H % 4,23; Found N % 10,68 C % 41,39 S % 12,22H % 4,17. the product extracted into CH2Cl2 (5×100 mL) The organic extracts were washed with water dried over MgSO4 evaporated to give an oily product The remaining DMF was removed by trituration with petrol The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1)

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

实验步骤: A solution of 2.6 g of sulphur dichloride in 15 ml of dry diethyl ether was added over 10 minutes to a stirred solution of 3.1 g of N-ethylmethanesulphonamide in 15 ml of the same solvent, keeping the temperature between 10°-15° by means of external cooling. A solution of 2.0 g of dry pyridine in 15 ml of dry diethyl ether was then added over 15 minutes at the same temperature and the reaction mixture was allowed to warm to room temperature over 1 hour. The resulting suspension was added over 5 minutes to a solution of 7.2 g of 4-[2-chloro-4-(trifluoromethyl)phenoxy]aniline (1A) in 75 ml of dry diethyl ether containing 2.0 g of pyridine, keeping the temperature of the mixture between 5°-10° C. After stirring at 10°-15° for 1 hour, the reaction mixture was washed three times with water, the ether layer was separated, dried (MgSO 4), and the solvent was evaporated under reduced pressure. The residue was purified by chromatography on silica gel using diethyl ether as eluent, to give 2, as a buff solid m.p.: 98°-101° C. between 10°-15° between 5°-10° C the reaction mixture was washed three times with water the ether layer was separated dried (MgSO 4) the solvent was evaporated under reduced pressure The residue was purified by chromatography on silica gel to give 2

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-ethyl-methanesulfonamide (Mijs et al. J.Chem.Soc.Chem.Com. 1972 p412) (5 g 40.6 mmol) was added to a suspension of sodium hydride (1.9 g, 55% in mineral oil) in anhydrous DMF (100 mL) under nitrogen. The mixture was warmed to 55° C. for one hour and 2,4-difluoronitrobenzene (4.4 mL) was added dropwise. The reaction was stirred at 60° C. overnight, poured into water (500 mL) and the product extracted into CH2Cl2 (5×100 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give an oily product. The remaining DMF was removed by trituration with petrol. The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1) to yield the desired product which was recrystallised from ethanol. Yield 3.5 g (33%). Calculated N % 10,68 C % 41,22 S % 12,23 H % 4,23; Found N % 10,68 C % 41,39 S % 12,22 H % 4,17. the product extracted into CH2Cl2 (5×100 mL) The organic extracts were washed with water dried over MgSO4 evaporated to give an oily product The remaining DMF was removed by trituration with petrol The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1)

反应条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-ethyl-methanesulfonamide (Mijs et al. J.Chem.Soc.Chem.Com. 1972 p412) (5 g 40.6 mmol) was added to a suspension of sodium hydride (1.9 g, 55% in mineral oil) in anhydrous DMF (100 mL) under nitrogen. The mixture was warmed to 55° C. for one hour and 2,4-difluoronitrobenzene (4.4 mL) was added dropwise. The reaction was stirred at 60° C. overnight, poured into water (500 mL) and the product extracted into CH2Cl2 (5×100 mL). The organic extracts were washed with water, dried over MgSO4 and evaporated to give an oily product. The remaining DMF was removed by trituration with petrol. The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1) to yield the desired product which was recrystallised from ethanol. Yield 3.5 g (33%). Calculated N % 10,68 C % 41,22 S % 12,23 H % 4,23; Found N % 10,68 C % 41,39 S % 12,22 H % 4,17. the product extracted into CH2Cl2 (5×100 mL) The organic extracts were washed with water dried over MgSO4 evaporated to give an oily product The remaining DMF was removed by trituration with petrol The crude product was purified by flash chromatography (ethyl acetate:petrol 1:1)