Methanesulfonyl chloride → 1-[Bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene] azetidine

Participants

Reaction Conditions

Reaction Steps

2.47 g of potassium tert-butoxide are added to a suspension of 6.12 g of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one and 5.15 g of methyl 5-(methylsulfonylmethyl)thiophene-2-carboxylate in 200 cm3 of tetrahydrofuran, under an argon atomosphere, cooled to −70° C. The mixture is stirred for 1 hour 30 min at a temperature close to −70° C., and then 1.7 cm3 of methanesulfonyl chloride in solution in 8 cm3 of ethyl ether is added. After stirring for 1 hour at a temperature close to −70° C., the mixture is allowed to return to room temperature and then 80 cm3 of distilled water are added. The mixture is concentrated in a rotary evaporator to one third of its initial volume, and is then extracted with 500 cm3 of dichloromethane. The organic phase is washed with three times 80 cm3 of distilled water, dried over magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is chromatographed on a silica gel column (particle size 0.02-0.04 mm, diameter 7.5 cm, height 35 cm), eluting at a nitrogen pressure of 0.5 bar with a cyclohexane and ethyl acetate mixture (70/30 by volume) and collecting 40 cm3 fractions. Fractions 19 to 29 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 1.6 g of 1-[bis(4-chlorophenyl)methyl]-3-[(methylsulfonyl)(2-methoxycarbonylthien-5-yl)methylene]azetidine are obtained in the form of a cream-colored foam [1H NMR spectrum (400 MHz, CDCl3, δ in ppm): 2.91 (s, 3H), 3.88 (s, 3H), 4.08 (mt, 2H), 4.37 (mt, 2H), 4.53 (s, 1H), from 7.25 to 7.45 (mt, 9H), 7.71 (d, J=3.5 Hz, 1H)].

Provenance & Evidence