Lithium Hexamethyldisilazide → Methyl 4-{2-(3-bromophenyl)-3-[(4-methoxybenzyl)oxy]-1-methyl-3-oxopropyl}benzoate

Participants

Reaction Steps

LHMDS (1.0M THF, 2.6 mL) was added dropwise to a −78° C. THF (4 mL) solution containing the intermediate from Step A (0.827 g, 2.47 mmol). After stirring 10 minutes a THF (4 mL) solution containing methyl 4-(1-bromoethyl)benzoate (0.6 g, 2.47 mmol) was added dropwise. The solution was allowed to warm to room temperature. After 1.5 hours the solution was partitioned between ethyl acetate and aqueous 1N HCl. The organic phase was washed with water, brine and dried over magnesium sulfate. The solution was filtered and the residue purified by silica gel chromatography using a hexanes/ethyl acetate gradient to give the title compounds as a 1.67/1 mixture of diastereomers. 1H NMR (400 MHz, CDCl3): selected data δ 5.16 (d, J=12.0 Hz); 5.01 (d, J=12.0 Hz); 4.82 (d, J=12.0 Hz); 4.64 (d, J=11.9 Hz); 1.34 (d, J=6.8 Hz); 1.02 (d, J=7.0 Hz). Minor diastereomer: LCMS1 4.08 min (M+Na)=519. Major diastereomer: LC1 4.19 min (M+Na)=519.

Provenance & Evidence