Triethylamine → (1R,2R)-N-(2,4,6-trimethylphenylsulfonyl)-1,2-diphenylethane-1,2-diamine

Participants

Reaction Conditions

Reaction Steps

A solution of 2,4,6-trimethylbenzene-1-sulfonyl chloride 31 (1.54 g, 7.06 mmol, 0.99 eq) in tetrahydrofuran (75 mL) was added drop-wise at 0° C. over 70 minutes (min) to a suspension of (1R,2R)-1,2-diphenylethane-1,2-diamine 30 (1.5 g, 7.08 mmol, 1.0 eq), triethylamine (2.04 g, 2.8 mL, 2.02 mmol, 0.28 eq) and powdered potassium carbonate (1.60 g, 11.59 mmol, 1.64 eq) in a mixture of tetrahydrofuran (60 mL) and N,N-dimethylformamide (15 mL). When addition was complete the suspension was stirred at 0° C. for 3 hours (h). The reaction mixture was concentrated under reduced pressure to remove most of the tetrahydrofuran. The residual oily solid was partitioned between water (100 mL) and 3:1 ethyl acetate/heptanes. The organic phase was diluted with heptanes (50 mL) and the solution washed with water (3×100 mL) followed by brine (100 mL). The organic solution was dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure to give a pale yellow oil. The crude product was dissolved in a minimum volume of dichloromethane, adsorbed onto silica gel and dry-loaded on a column of silica gel (50 g) packed in 75% ethyl acetate/heptanes. The column was eluted with 75% ethyl acetate/heptanes (300 mL) and ethyl acetate (300 mL). Product-containing fractions were concentrated under reduced pressure to give a slightly gummy solid that was triturated with hexanes containing a small amount of methyl t-butyl ether, filtered, washed with hexanes and dried to give 1.90 g of 32 as a white solid.

Provenance & Evidence