Methyl iodide → N-tert-butyl-1-methylcyclopropane-1-sulfonamide

Participants

Reaction Conditions

Reaction Steps

To a four necked, 5 L round bottom flask was added N-(tert-butyl)-3-chloropropane-1-sulfonamide (Previously dried by azeotroping with 3×100 mL toluene) (100 g, 468 mmol) and THF (1500 mL). This was cooled to an internal temperature of −69° C. then butyl lithium (2.5M in hexanes, 412 mL, 1.02 mol) was added dropwise over a period of 55 min while keeping the internal temperature below −65° C. The ice bath was removed and the reaction mixture was warmed to rt over 1.5 h and then cooled back down to an internal temperature of −69° C. Butyl lithium (196 mL, 515 mmol) was added to the reaction mixture over a period of 25 min while keeping the internal temperature below −65° C. The reaction mixture was then warmed to rt over the course of 1.5 h. The reaction mixture was recooled to an internal temperature of −69° C. and iodomethane (58.5 mL, 936 mmol) was added dropwise over a period of 40 min while keeping the internal temperature below −65° C. The reaction mixture was then warmed to an internal temperature of −50° C. over the course of 4 h. The cold bath was removed and a solution of saturated NH4Cl (1000 mL) was added. The quenched reaction mixture was transferred to a separatory funnel along with ethyl acetate (100 mL) and water (500 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate. (3×75 mL). The combined organic layers were washed with brine (700 mL), dried with MgSO4, and concentrated in vacuo to an off white solid which was dried under high vac for 30 min to yield N-(tert-butyl)-1-methylcyclopropane-1-sulfonamide as a white solid (88.5 g, 99% yield). 1H NMR (500 MHz, CDCl3) δ 4.07 (bs, 1 H), 1.51 (s, 3 H), 1.38-1.41 (m, 2 H), 1.36 (s, 9 H), 0.77-0.80 (m, 2 H).

Provenance & Evidence