Methylamine → HCID 15942617, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of [(2R)-8-(2,6-dichlorophenyl)-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate, prepared in Example 35, step 7 (0.33 g, 0.715 mmol) in anhydrous dimethyl sulfoxide (1.2 mL) was added a solution of methylamine (2.0 M in tetrahydrofuran, 3.58 mL, 7.15 mmol) and the mixture heated at 60° C. in a sealed vial for 26 hours. The cooled reaction mixture was then poured into 1:1 v/v 2.0 M aqueous sodium hydroxide solution:saturated brine (50 mL) and the product extracted with ethyl acetate (50 mL). The separated organic extract was washed with 1:1 v/v 2.0 M aqueous sodium hydroxide solution:saturated brine (50 mL), and half saturated brine (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford a brown syrup. Purification by flash chromatography using a solvent gradient of 0 to 5% ammonia saturated methanol solution in dichloromethane gave 160 mg (70%) of {[(2R)-8-(2,6-dichlorophenyl)-2H-chromen-2-yl]methyl}methylamine as a yellow syrup. The product was dissolved 2-propanol (1.5 mL) and diethyl ether (3 mL) and a solution of hydrogen chloride (1.0 M in diethyl ether, 0.36 mL, 0.36 mmol) was added followed by hexane (4 mL). The resulting white precipitate was filtered to afford 121 mg (47%) of {[(2R)-8-(2.6-dichlorophenyl)-2H-chromen-2-yl]methyl}methylamine hydrochloride as a tan solid. HRMS: calcd for C17H15Cl2NO+H+, 320.06034. found (ESI, [M+H]+), 320.0619.

Provenance & Evidence