Chlorotrimethylsilane → HCID 21079666, compound
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[F:8].[CH3:9][Si:10](Cl)([CH3:12])[CH3:11].C([Li])CCC>>[F:1][C:2]1[C:3]([F:8])=[C:4]([Si:10]([CH3:12])([CH3:11])[CH3:9])[CH:5]=[CH:6][C:7]=1[Si:10]([CH3:12])([CH3:11])[CH3:9]Participants
Procedure
4-Alkoxy-2-fluoro-3-phenoxyphenylacetic acid compounds were prepared from o-difluorobenzene. A mixture ortho-difluorobenzene (54a) and trimethylsilylchloride was treated with butyl lithium to produce 2,3-difluoro-1,4-bis-trimethylsilanyl-benzene (54b) which was brominated to afford 54c. Selective monometallation of 54c with iso-propylmagnesium chloride-lithium chloride complex and quenching the organomagnesium compound with DMF afforded 54d. Reaction of 54d with a phenol in the presence of K2CO3 resulted in displacement of the fluorine atom adjacent to the aldehyde to afford 56a. The aldehyde was subjected to a Baeyer-Villiger oxidation with trifluoroperacetic acid which underwent concomitant hydrolysis to the phenol 56b which was alkylated with Cs2CO3 and methyl iodide to afford the methoxy substituted analog 56c. Metallation of the remaining bromine substituent with iso-PrMgCl/LiI/THF and allylation of the resulting Grignard reagent afforded 58a which was oxidatively cleaved with NaIO4/Ru(III)Cl3 to produce the phenylacetic acid 58b.
Sources & evidence
- ORD record
- ord-a72e59335ffe4923897516b0335acbf9
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07625949B2
Reaction notes
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