Triethyl 2-fluoro-2-phosphonoacetate → (2Z,4E,6E)-2,6-difluoro-3-methyl-7-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-octa-2,4,6-trienoic acid ethyl ester

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Reaction Steps

Following General Procedure B and using triethyl 2-fluoro-2-phosphonoacetate (0.3 mL, 1.44 mmol), THF (4 mL), n-BuLi (0.9 mL, 1.6 M in hexane, 1.44 mmol), (3E,5E)-5-fluoro-6-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-hepta-3,5-dien-2-one (Intermediate 9, 177 mg, 0.48 mmol) in THF (2 mL) at −78° C. for overnight, the title compound and its 2-E isomer were obtained by flash column chromatography on silica gel (3% EtOAc-hexane) as a ˜1.4:1 mixture (222 mg). Further purification by HPLC (2.5% EtOAc-hexane) afforded the title compound as a clear oil (102 mg, 47%).

Provenance & Evidence