methyl 2-chlorosulfonylacetate

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:

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:

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:

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: Chlorine gas was passed through a suspension of 230 g of ice, CH2Cl2 (457 ml) and methyl thioglycolate (86 ml, 942 mmol), cooling with an ice/water bath to maintain an internal temperature below 30° C. After approximately six hours, the yellow/green color of the dissolved chlorine persisted for 30 minutes after gas flow was stopped and passing additional chlorine gas was no longer exothermic. The cooling bath was then removed and the biphasic mixture was allowed to stir at ambient temperature for 1 h before being sparged with nitrogen for 20 minutes. The layers were then separated and the organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure to provide the intermediate methyl (chlorosulfonyl)acetate (160 g, 927 mmol) as a yellow oil. A portion of the intermediate methyl (chlorosulfonyl)acetate (100 g, 579 mmol) was added dropwise as a solution in CH2Cl2 (290 ml) to a stirring −15° C. solution of N-methylaniline (124 g, 1159 mmol) dissolved in CH2Cl2 (290 ml). The rate of addition was adjusted to maintain the internal temperature below 5° C. After the addition was complete, the reaction mixture was allowed to warm to room temperature over the course of 2 h and 1 M HCl (1000 mL) was added and the aqueous phase was extracted with dichloromethane (2×500 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting oil was seed crystallized to afford a brown solid. Recrystallization from hot ethanol (320 mL) provided the title compound as an off-white solid. 1H NMR (600 MHz, DMSO-D6) δ 7.40 (m, 4H); 7.31 (m, 1H); 4.30 (s, 2H); 3.65 (s, 3H); 3.26 (s, 3H). LRMS (APCI) calculated for C25H21N4O3S [M+H]+, 244.1; found 244.0. The rate of addition to maintain the internal temperature below 5° C After the addition was added the aqueous phase was extracted with dichloromethane (2×500 mL) The combined organics were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure crystallized to afford a brown solid Recrystallization from hot ethanol (320 mL)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dimethylamine in THF (57.9 ml, 116 mmol) was dissolved in dichloromethane (29.0 ml) and cooled to 0° C. Then, methyl (chlorosulfonyl)acetate (prepared according to: Szymonifka, M. J.; Heck, J. V. Tet. Lett. 1989, 30, 2869-72.) (10.0 g, 57.9 mmol) was added dropwise as a solution in dichloromethane (29.0 ml), while maintaining the temperature below 5° C. The resulting solution was allowed to warm to room temperature over the course of 2 h. Then, brine (200 mL) was added and the aqueous phase was extracted with dichloromethane (3×100 mL). The combined organics were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (EtOAc/Hexanes gradient) to afford the title compound as a yellow liquid. 1H NMR (600 MHz, DMSO-D6) δ 4.25 (s, 2H); 3.68 (s, 3H); 2.78 (s, 6H). LRMS (APCI) calculated for C5H12NO4S [M+H]+, 182.0; found 182.0. while maintaining the temperature below 5° C to warm to room temperature over the course of 2 h the aqueous phase was extracted with dichloromethane (3×100 mL) The combined organics were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was purified by column chromatography on silica gel (EtOAc/Hexanes gradient)