Methyl Acetate → (S)-methyl 3-(5-bromo-2-fluorophenyl)-3-((R)-1,1-dimethylethylsulfinamido)-4-fluorobutanoate

Participants

Reaction Conditions

Reaction Steps

A flame dried RBF equipped with an addition funnel was charged with DIPA (9.32 ml, 66.5 mmol, Aldrich) and THF (70 ml). The solution was cooled to 0° C. before adding a solution of n-butyllithium (2.5M in hexanes; 26.8 ml, 67 mmol, Aldrich) drop wise. The reaction was stirred at 0° C. for 15 minutes then cooled to −78° C. A solution of methyl acetate (4.9 g, 66.5 mmol, Aldrich) in THF (25 ml) was added dropwise via cannula to the LDA solution at −78° C. After 30 minutes, a solution of chlorotitanium triisopropoxide, (18.5 g, 71.0 mmol, Aldrich) in THF (70 ml) was added drop wise via cannula and the reaction was stirred at −78° C. After 1 h, a solution of (R)—N-(1-(5-bromo-2-fluorophenyl)-2-fluoroethylidene)-2-methylpropane-2-sulfinamide (15.0 g, 27.1 mmol, step 3) in THF (100 ml), was added drop wise via cannula at −78° C. and the reaction was stirred at −78° C. for 45 minutes. The reaction was quenched with aqueous, saturated ammonium chloride solution, diluted with water and EtOAc and stirred vigorously for 20 minutes. The reaction was filtered through celite and the filter cake was washed with additional EtOAc. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated under reduced pressure. The crude material was purified via silica gel flash chromatography using a solvent gradient of 10-60% acetone in hexanes to afford the title compound as a light yellow oil (12.0 g, 29.1 mmol, 65.6% yield, dr: 97:3 by LC/MS). MS m/z=411.9 M+. Calculated for C15H20BrF2NO3S: 412.290

Provenance & Evidence