Chlorotrimethylsilane → HCID 21079666, compound

Participants

Reaction Steps

4-Alkoxy-2-fluoro-3-phenoxyphenylacetic acid compounds were prepared from o-difluorobenzene (SCHEME 5). A mixture ortho-difluorobenzene (23a) and trimethylsilylchloride was treated with butyl lithium to produce 2,3-difluoro-1,4-bis-trimethylsilanyl-benzene (23b) which was brominated to afford 23c. Selective monometallation of 23c with iso-propylmagnesium chloride-lithium chloride complex and quenching the organomagnesium compound with DMF afforded 23d. Reaction of 23d with a phenol in the presence of K2CO3 resulted in displacement of the fluorine atom adjacent to the aldehyde to afford 24a. The aldehyde was subjected to a Baeyer-Villiger oxidation with trifluoroperacetic acid which underwent concomitant hydrolysis to the phenol 24b which was alkylated with Cs2CO3 and methyl iodide to afford the methoxy substituted analog 24c. Metallation of the remaining bromine substituent with iso-PrMgCl/LiI/THF and allylation of the resulting Grignard reagent afforded 25a which was oxidatively cleaved with NaIO4/Ru(III)Cl3 to produce the phenylacetic acid 25b.

Provenance & Evidence