Water → (S)-tert-Butyl 4-(1-amino-3-(4'-cyanobiphenyl-4-yl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (S)-tert-butyl 4-(1-amino-3-(4-iodophenyl)-1-oxopropan-2-ylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (produced in step (i), 27 g) in 2-methyltetrahydrofuran (8 rel. vol.) was added 4-cyanophenyl boronic acid (1.1 mol. eq.), potassium carbonate (2 mol. eq.), water (2 rel. vol.) and 1,1 bis(di-tert-butylphosphino)ferrocene palladium dichloride (0.0065 mol. eq) at room temperature. Reaction mixture was heated to 78° C. and stirred for 10 h under nitrogen. The reaction mixture was cooled to room temperature and passed through a pad of celite. Water was added to the mixture and the layers separated. The organic layer was separated and concentrated to 5 rel. vol. under vacuum. The concentrated organic portion was stirred for 6 h at room temperature and the resulting solid filtered and washed with 2-methyltetrahydrofuran (2 rel. vol.). The solid was dried at 50° C. under vacuum to afford the sub-titled compound (17.3 g).

Provenance & Evidence