Sodium Carbonate → HCID 67244310, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of (R)-1-(4-bromophenyl)ethylamine (23.89 g, 0.101 mol) in tetrahydrofuran (200 ml) was added triethylamine (21 ml), 4-dimethylaminopyridine (1.5 g) and di-tert-butyldicarbonate (26.5 g, 0.121 mol). The solution was stirred overnight then diluted with diethyl ether and washed with 2M aqueous hydrogen chloride solution, 10% aqueous sodium carbonate solution and brine. The organic phase was dried over anhydrous sodium sulfate and the solution concentrated to low volume. Heptane was added and the resulting white solid filtered off and dried to give (R)-[1-(4-bromophenyl)-ethyl]-carbamic acid tert-butyl ester (17 g). To a solution of (R)-[1-(4-bromophenyl)-ethyl]-carbamic acid tert-butyl ester (2 g, 6.7 mmol) in toluene (40 ml) was added 5-chloro-2-methoxypyridine boronic acid (2.5 g, 13.3 mmol), 2M aqueous sodium carbonate solution (6.8 ml) and tetrakis(triphenylphosphine) palladium (0) (0.4 g). The solution was heated under reflux for 48 h then washed with water, brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue dissolved in dichloromethane (50 ml) and the solution cooled to 0° C. Trifluoroacetic acid (20 ml) was added and the solution stirred for 3 h then evaporated to a gum which was chromatographed on a SCX column eluting with methanol then ammonia/methanol. The solvent was removed and the residue flash chromatographed on silica eluting with 9:1 dichloromethane/methanol then 9:1 dichloromethane/methanol-ammonia. The solvent was evaporated to give (R)-1-[4-(5-chloro-2-methoxy-pyridin-3-yl)-phenyl]-ethylamine (1.37 g) as a gum.

Provenance & Evidence