F. J. Urban, V. J. Jasys
Mar 1, 2004
Citations
0
Influential Citations
12
Citations
Journal
Organic Process Research & Development
Abstract
Two processes for the preparation of lactone [2S-(3-fluorophenyl)-1S-(5-oxotetrahydrofuran-2-yl)ethyl]carbamic acid tert-butyl ester 1 starting from S-BOC-(3-fluorophenyl)alanine 3 are described. (S)-(3-Fluorophenyl)alanine N-methyl-N-methoxy amide 10, the Weinreb amide of 3, was reacted with 2-(2-1,3-dioxanyl)ethylmagnesium bromide to provide key intermediate ketoacetal 11. To achieve high yields for this conversion, the N−H of the BOC group in Weinreb amino acid amide 10 was deprotonated first with a simple Grignard reagent (methyl or benzylmagnesium halide) followed by Barbier reaction with magnesium metal and 2-(2-bromoethyl)-1,3-dioxane. The acetal group in 11 was opened oxidatively with ozone, and the resulting ester 15 was reduced selectively at low temperature with N-Selectride. Alternatively, the ketone moiety in 11 was reduced diastereoselectively with aluminum triisopropoxide in 2-propanol to give the undesired (R,S)-diastereomeric alcohol. The alcohol was converted to the mesylate which was he...