| 主权项 |
1. A process for the preparation of N-(1-oxopentyl)-N-[[2′-(1H-tetrazol-5-yl)(1,1′-biphenyl-4-yl]methyl]-L-valine of Formula 1, which comprises: i. reacting a 4-halomethyl 2′-(1-protected-tetrazol-5-yl)biphenyl compound of Formula 3 where X is a halogen and Q is H or a Nitrogen protecting Group with a L-valine ester of Formula-2 where R is a carboxylic acid protecting group selected from substituted or unsubstituted C1-C6 alkyl group, substituted or unsubstituted aryl group, aralkyl group and the like to afford a compound of formula-4ii. converting the compound of formula-4 to its phosphite salt of Formula-4.H3PO3iii. preparing a compound of Formula-5by
a) optionally treating the compound of formula-4.H3PO3 with a base in a solvent followed by reacting with n-valeroyl chloride in the presence of a base in a solvent to produce a compound of formula-5, OR b) directly reacting a compound of formula-4.H3PO3 with n-valeroyl chloride in the presence of a base in a solvent to produce N-[2′-1-protected-tetrazol-5-yl)biphenyl-4-yl)methyl]-N-valeroyl-(L)-valine ester of formula-5, iv. de-protecting the compound of Formula-5 to afford N-(1-oxopentyl)-N-[[2′-(1H-tetrazol-5-yl) (1,1′-biphenyl-4-yl]methyl]-L-valine of Formula 1. |
