Water → 1035662-71-5

Participants

Reaction Steps

Water (2.6 ml) is added to the stirred solution (10.5 ml) of N-[(E)-(R)-1-(3,4-dichloro-benzyl)-3-((R)-2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (12) in methanol at approx. 18-22° C., whereupon crystallisation begins. After stirring for approx. 10 minutes, water (1 ml) is added at 18-22° C. over a period of approx. 20 minutes. Stirring at 18-22° C. is continued for 2 hours. The precipitated solids are isolated by filtration and the filter cake is rinsed with a mixture of methanol and water (2 ml+1 ml), followed by water (3 ml). The solids are dried at 30° C. in vacuo to constant weight to yield N-[(E)-(R)-1-(3,4-dichloro-benzyl)-3-((R)-2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide hemihydrate (13) [1.6241b=85.5% of theory based on (E)-(R)-5-(3,4-dichloro-phenyl)-4-methylamino-pent-2-enoic acid ((R)-2-oxo-azepan-3-yl)-amide (10)], m.p. 127-131° C., sintering >123° C., MS-ES+: (MH)+=624 (35Cl2), [α]D20=+40.6° (methanol).

Provenance & Evidence