2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 131732969, compound

Participants

Reaction Conditions

Reaction Steps

A 250 mL round bottomed flask was charged with N-[5-bromo-4-(2-hydroxyethyl)pyridin-2-yl]-2,2-dimethylpropanamide (1.9 g, 6.31 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.173 g, 0.189 mmol), and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (0.180 g, 0.379) and the mixture was flushed with nitrogen for 30 min. tetrahydrofuran was added, followed by a solution of 2-tert-butoxy-2-oxoethylzinc chloride in diethyl ether (0.5 M, 47.9 mL) and the mixture was placed in an oil bath maintained at 45° C. After 12 h, the reaction was recharged with tris(dibenzylideneacetone)dipalladium(0) (0.173 g, 0.189 mmol) and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (0.180 g, 0.379) and an additional quandity of 2-tert-butoxy-2-oxoethylzinc chloride in diethyl ether (0.5 M, 12.6 mL) was added. After stirring an additional 2 h in the 45° C. bath, the reaction mixture was diluted with ethyl acetate and 10% ammonium hydroxide solution, filtered to remove solids, and the layers separated. The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated. Purification by MPLC (eluent 9-90% ethyl acetate/hexanes) afforded tert-butyl{6-[(2,2-dimethylpropanoyl)amino]-4-(2-hydroxyethyl)pyridin-3-yl}acetate. 1H NMR (500 MHz, CDCl3), δ 8.30 (br s, 1H), 8.17 (s, 1H), 7.99 (s, 1H), 3.88 (dd, J=6.5, 6.5 Hz, 2H), 3.55 (s, 2H), 2.88 (dd, J=6.5, 6.5 Hz, 2H), 1.40 (s, 9H), 1.28 (s, 9H); LC/MS (M+1)+=337.0;

Provenance & Evidence