Convenient Preparation of 2-Phenylethyl 3,3-Difluoro-2-methylpropionate

Abstract

The slow inverse addition of an LDA solution at -78 °C to an ester of 2-(trifluoromethyl)acrylic acid enabled efficient dehydrofluorination. Hydrogenation of the resulting difluoromethylacrylate furnished the target ester of 3,3-difluoro-2-methylpropionic acid in good overall yield.

A Novel Prosthetic Group for Site-Selective Labeling of Peptides for Positron Emission Tomography

“…In recent years, 18 F-labeled peptides have gained increasing interest as an important class of radiotracer well-suited to functional imaging with PET (1-3). The intrinsic pharmacokinetic properties, high affinity, and versatility of solid-phase chemistry make small proteins and peptides attractive candidates for diagnostic imaging.…”

“…Although direct labeling routes have been described (4), the most common method utilizes a two-step process whereby the fluorine-18 is first introduced into a prosthetic group followed by conjugation to the peptide. This strategy separates the harsh reaction conditions required for [ 18 F]fluoride incorporation from the mild conditions preferred for conjugation, ameliorating the risk of significant degradation of the peptide precursor. A variety of 18 F-labeled prosthetic groups have been developed for incorporation into peptides, exploiting many different chemical reactions.…”

“…This strategy separates the harsh reaction conditions required for [ 18 F]fluoride incorporation from the mild conditions preferred for conjugation, ameliorating the risk of significant degradation of the peptide precursor. A variety of 18 F-labeled prosthetic groups have been developed for incorporation into peptides, exploiting many different chemical reactions. These include acylation, alkylation, oxime formation, hydrazone formation, and 1,3-dipolar cycloaddition (4-7).…”

“…These include acylation, alkylation, oxime formation, hydrazone formation, and 1,3-dipolar cycloaddition (4-7). Although alkylation and Michael-type reactions are often used in conjugation chemistry, there are limited cases reported for peptide labeling with 18 Fcontaining prosthetic groups. Examples include the [ 18 F]thiol conjugation to R-haloacetylated or maleimide-modified peptides and [ 18 F]maleimide conjugation to peptides bearing a free thiol group (7,8).…”

In Situ Generation of 3,3,3-Trifluoropropanal and Its Use for Carbon−Carbon Bond-Forming Reactions

“…General Procedure for Reaction of 2-Phenylethyl 2-Methyl-3,3,3-trifluoropropionate 2 by Way of Aluminum Acetal Intermediate 3. To an ethereal solution (5 mL) of 2-phenylethyl 2-methyl-3,3,3-trifluoropropionate 2 (246 mg, 1.00 mmol) was added at −78 °C a 1 mol/L hexane solution of DIBAL (1.05 mL, 1.05 mmol), and the mixture was stirred for 0.5 h at that temperature. An appropriate nucleophile (2.00 mmol), preformed alkylmetals or enolates by the conventional methods, was added to this solution, and after changing the dry ice−acetone bath to an ice bath, the whole solution was stirred for 1.5 h at 0 °C.…”