1-METHYL-CYCLOPROPANESULFONIC ACID TERT-BUTYLAMIDE

63132-85-4

74-88-4

669008-25-7

General procedure for the preparation of N-tert-butyl-1-methylcyclopropane-1-sulfonamide: N-tert-butyl-3-chloropropane-1-sulfonamide (100 g, 468 mmol), which was pre-dried by azeotropy with 3 x 100 mL of toluene, was dissolved in THF (1500 mL). The solution was cooled to an internal temperature of -69 °C, followed by the dropwise addition of butyllithium (2.5 M hexane solution, 412 mL, 1.02 mol) over 55 min while ensuring that the internal temperature remained below -65 °C. The ice bath was removed and the reaction mixture was slowly warmed to room temperature over 1.5 hr and then cooled again to an internal temperature of -69°C. Butyl lithium (196 mL, 515 mmol) was added to the reaction mixture over 25 minutes while maintaining the internal temperature below -65°C. Subsequently, the reaction mixture was warmed to room temperature over 1.5 hours. The reaction mixture was again cooled to an internal temperature of -69 °C and iodomethane (58.5 mL, 936 mmol) was added dropwise over 40 min while controlling the internal temperature below -65 °C. The reaction mixture was heated to an internal temperature of -50 °C over 4 hours. The cold bath was removed and quenched by adding saturated NH4Cl solution (1000 mL). The quenched reaction mixture was transferred to a dispensing 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 x 75 mL). The organic layers were combined, washed with brine (700 mL), dried over MgSO4 and concentrated in vacuum to give an off-white solid. The solid was dried under high vacuum for 30 min to give 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, 1H), 1.51 (s, 3H), 1.38-1.41 (m, 2H), 1.36 (s, 9H), and 0.77-0.80 (m, 2H).