Lithium diisopropylamide → (E)-2-Fluoro-3-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-but-2-enoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of LDA (12.1 mL, 2.0 M in heptane/THF/ethylbenzene) in THF (10 mL) at −78° C. was added triethyl 2-fluoro-2-phosphonoacetate (5.0 g, 20.7 mmol) in THF (10 mL). The reaction flask was removed from dry ice cooling bath for 12 min and then re-cooled to −78° C. 1-(5,5,8,8-tetramethyl-3-propoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone (Intermediate 5, 1.98 g, 6.89 mmol) in THF (10 mL) was added and the reaction was allowed to warm up to ambient temperature over night. The reaction was quenched with aqueous NH4Cl and extracted with Et2O (×3). The combined organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (3% EtOAc-hexane) to give a ˜10:1 mixture of the title compound and its 2-Z isomer (2.2 g). The mixture was used directly in the next reaction.

Provenance & Evidence