Methylamine → HCID 59701576, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of [(2R)-8-(2,6-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate (239 mg, 0.54 mmol) in anhydrous dimethyl sulfoxide (1 mL) was added a solution of methylamine (2.0 M in tetrahydrofuran, 2.7 mL, 5.4 mmol) and the mixture heated to 60° C. in a sealed vial for 42 hours. The cooled reaction mixture was then poured into 1:1 v/v 2.0 M aqueous sodium hydroxide and saturated brine (50 mL) and the mixture extracted with ethyl acetate (50 mL). The separated organic phase was washed with 1:1 v/v 2.0 M aqueous sodium hydroxide and saturated brine (50 mL), and half saturated brine (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a yellow syrup. Purification by flash chromatography using a solvent gradient of 0.5 to 5% ammonia saturated methanol solution in dichloromethane gave 125 mg (75%) of {[(2R)-8-(2,6-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}methylamine as a white solid. The product was dissolved in 2-propanol (1 mL) and diethyl ether (2.5 mL) and a solution of hydrogen chloride (1.0 M in diethyl ether, 0.39 mL, 0.39 mmol) was added followed by hexane (3 mL). The resulting white precipitate was filtered to afford 118 mg (64%) of {[(2R)-8-(2,6-dichlorophenyl)-3,4-dihydro-2H-chromen-2-yl]methyl}methylamine hydrochloride as a white crystalline solid. HRMS: calcd for C17H17Cl2NO+H+, 322.07599; found (ESI, [M+H]+), 322.0757.

Provenance & Evidence