(S)-tert-Butyl 4-(1-cyano-2-(4'-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate → 4-Amino-N-[(1S)-1-cyano-2-(4'-cyano[1,1'-biphenyl]-4-yl)ethyl]tetrahydro-2H-pyran-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

To (S)-tert-butyl 4-(1-cyano-2-(4′-cyanobiphenyl-4-yl)ethylcarbamoyl)tetrahydro-2H-pyran-4-ylcarbamate (produced in step (iii), 5 g) was added formic acid (6 rel. vol.) at room temperature and the mixture heated to 40° C. The reaction mixture was stirred for 1.5 h at 40° C. and then cooled to 0-8° C. and quenched with water (5 rel. vol.). The reaction mixture was diluted with 2-methyltetrahydrofuran (10 rel. vol.) and 2N NaOH solution added dropwise at 0-8° C. until the pH reached 6.7. The reaction mixture was further diluted with 2-2-methyltetrahydrofuran (10 rel. vol.) and extracted. The organic layer was separated and concentrated to 8 rel. vol. under vacuum. The mixture was stirred the concentrated for 1 h at room temperature and the resulting solid was filtered and washed with 2-methyltetrahydrofuram (1 rel. vol.) to afford the titled compound (2.0 g).

Provenance & Evidence