Tetrahydrofuran → HCID 86653899, compound

Participants

Reaction Conditions

Reaction Steps

(S)-2-amino-3-(4-(2-amino-6-((R)-2,2,2-trifluoro-1-(3′-methoxybiphenyl-4-yl)ethoxy)pyrimidin-4-yl)phenyl)propanoate (120.0 g, 88 w %, 105.6 g active, 196 mmol) was added to a solution of TsOH.H2O (39.8 g, 209 mmol) in a mixture of THF (240 mL) and water (48 mL). The mixture was heated to 50° C. to give a homogeneous solution. Approximately 120 mL of a mixture of ACN/water (1200/60 mL) was added and the mixture was seeded with (S)-2-amino-3-(4-(2-amino-6-((R)-2,2,2-trifluoro-1-(3′-methoxybiphenyl-4-yl)ethoxy)pyrimidin-4-yl)phenyl)propanoate tosylate dihydrate (0.63 g). After aging for 1 hour at 40° C., a nice slurry was obtained. The remaining ACN/water mixture was added slowly over 3 hours at 40° C. and the slurry was aged at 40° C. for 2 hours then slowly cooled to 20° C. and aged overnight. The solid was collected by filtration and the filter cake was washed with 5/1 ACN/THF with ˜5 vol % water (500 mL). Air drying at room temperature overnight gave 138.5 g of the product as a white solid (99.5 A %, 93.4% yield corrected for purity). Loss in the mother liquor and wash was 6.5%. KF of solid was 4.4%.

Provenance & Evidence