144156-84-3

Upstream product

• 100-51-6 benzyl alcohol 
• 1026150-41-3 2-Benzyloxy-3,3,3-trifluoro-2-hydroxy-propionic acid ethyl ester 
• 168101-89-1 ethyl 2-(benzyloxy)-2-chloro-3,3,3-trifluoropropanoate 
• 13081-18-0 ethyl-3,3,3-trifluoropyruvate 
• 168101-95-9 ethyl 2-(benzyloxy)-3,3-difluoropropenoate 
• 144156-83-2 Ethyl 3,3-difluoro-2-hydroxy-4-phenylbutanoate 

Downstream Products

• 144156-85-4 3,3-Difluoro-2-oxo-4-phenylbutanoic acid 

Relevant academic research and scientific papers

Conversion of α-keto esters into β,β-difluoro-α-keto esters and corresponding acids: A simple route to a novel class of serine protease inhibitors

The preparation of a series of β,β-difluoro-α-keto esters and corresponding acids RCF2COCO2R' (R=Me, Et, i-Pr, Bn, and Ph; R'=Et and H), designed as potential inhibitors of serine proteases, is described. The standard procedure developed consists in the initial formation of an α,α- difluoro ester from an α-keto ester, followed by a simple four-step sequence involving the synthesis of hemiacetal, cyanohydrin, and α-hydroxy ester difluorinated intermediates. This method provides an easy route to β,β- difluoro-α-keto esters and corresponding acids, via 'formal' insertion of a difluoromethylene group between the R substituent and the α-carbonyl group of a generic α-keto ester.

δ,ε-Unsaturated β,β-Difluoro-α-keto Esters: Novel Synthesis and Utility as Precursors of β,β-Difluoro-α-amino Acids

Treatment of the hemiketals 6 formed from ethyl trifluoropyruvate and primary allylic alcohols with SOCl2 and pyridine readily afforded a number of α-chloro-β,β-trifluorolactyl allyl ethers 2.Subsequent reductive dechlorofluorination from 2 led to the formation of allyl-substituted difluoroenol pyruvyl ethers 3 whose Claisen rearrangement provided a convenient access to a variety of δ,ε-unsaturated β,β-difluoro-α-keto esters 4.As further transformation, direct conversion of β,β-difluoro-α-keto esters to the corresponding β,β-difluoro-α-amino acids was achieved by reductive amination of the corresponding α-keto acids with NH3*H2O/NaBH4.Furthermore, use of the prepared β,β-difluoro-α-keto ester 4a as a common precursor of other structurally related β,β-difluoro-α-amino acids was demonstrated by the synthesis of β,β-difluoroproline (18) and β,β-difluoroglutamic acid (23) through synthetic elaboration of its inherent double bond.