4-Toluenesulfonyl chloride → [(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate

Participants

Reaction Conditions

Reaction Steps

To a solution of [(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methanol (5.00 g, 25.7 mmol) in dichloromethane (250 mL) is added p-toluenesulfonyl chloride (9.82 g, 51.5 mmol), 4-(dimethylamino)pyridine (0.62 g, 5.15 mmol), and N,N-diisopropylethylamine (8.32 g, 64.4 mmol) and the reaction mixture is heated to 50° C. for 12 h. The reaction mixture is quenched by the addition of water (500 mL). The aqueous layer is separated and extracted with dichloromethane (200 mL). The combined organic extracts are washed with aqueous hydrogen chloride (1.0 M, 200 mL), water (200 mL), aqueous sodium chloride (200 mL), dried (magnesium sulfate), and the solvent is removed in vacuo to provide a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 2:3) provides 6.45 g (72%, 40% ee) of [(2R)-8-methoxy-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate as a white crystalline solid. [α]D25=−20.30 (c 13.1 in chloroform, 40% ee); Rf=0.71 (silica, ethyl acetate:hexanes 2:3); mp 115-117° C.; Anal. Calcd. for C18H20O5S: C, 62.05; H, 5.79. Found: C, 61.99; H, 5.81.

Provenance & Evidence