Phenol → Ethyl 3-hydroxy-4-methylphenylacetate

Participants

Reaction Steps

Ethyl 3-hydroxy-4-methylphenylacetate (5a) was prepared from ethyl 3-methoxy-4-hydroxy-phenylacetate as shown in Scheme 2. The phenol was converted to the triflate ester 4b which was subjected to displacement with Me2Zn, DIBAL-H and PdCl2(dppf) (E.-i. Negishi in Metal-catalyzed Cross-Coupling Reactions, F. Diederich and P. J. Stang (eds.), Wiley-VCH, Mannheim 1998, chap. 1; E. Erdik, Tetrahedron 1992 48:9577–9648) to afford the 4c. Boron tribromide demethylation afforded 5a. Ethyl 3-hydroxy-4-ethylphenylacetate 5b was prepared by Friedel-Crafts acylation of 4d which afforded ethyl 4-acetyl-3-methoxyphenylacetate (4e). Reduction of the ketone with triethylsilane and TFA produced the corresponding 4-ethyl substituted derivative 4f which was demethylated with BBr3 to afford 5b. Ethyl 3-hydroxy-4-iso-propylphenylacetate (5c) was prepared by Wittig olefination of 4e and subsequent catalytic hydrogenation of the 2-propenyl substituent to yield 4h. Demethylation with boron tribromide produced 5c.

Provenance & Evidence