Divinyl sulfone → Thiomorpholine, 4-(2,6-difluorophenyl)-, 1,1-dioxide

Participants

Reaction Conditions

Reaction Steps

Aluminum chloride (310 g, 2.3 mol) was added to chlorobenzene (2.5 L) to give a cloudy green suspension. Vinyl sulfone (230 mL, 2.3 mol) was added via funnel, followed by 2,6-difluoroaniline (250 mL, 2.3 mol). The light brown solution was heated to 110° C. Upon completion of the reaction, the heat was removed and the black solution was self-cooled to 70° C. The reaction mixture was then quenched in methylene chloride (4 L) and ice water (5 L), the aqueous phase was extracted with methylene chloride (3 L, 2 L, 2 L, 2 L) and the combined organic layers are concentrated, rediluted with branched octane (3 L), and then cooled to 0° C. for 30 minutes. The solids are filtered and washed with branched octane (2×500 mL) and are then dissolved in methylene chloride (3 L) and loaded onto a SiO2 plug (1.8 kg). The column was eluted with dichloromethane (16 L) until clear. The methylene chloride solution was concentrated, and the solids are dissolved in hot ethyl acetate (3 L) followed by the addition of hexanes (900 mL). The black solution was self-cooled to room temperature overnight, and the resulting light amber crystal needles are filtered and washed with hexanes (4×250 mL). The solids are dried under reduced pressure at 50° C. overnight to give the title compound, 1H NMR (CDCl3) (δ): 7.08 (m, 1H), 6.91 (m, 2H), 3.67 (m, 4H), 3.18 (m, 4H).

Provenance & Evidence