Methyl Acetate → HCID 68153908, compound

Participants

Reaction Conditions

Reaction Steps

To a 0° C. solution of N,N-diisopropylamine (12.7 mL, 90.8 mmol) in THF (120 mL) was added n-butyllithium (2.5 M in hexanes, 35.1 mL) over ˜5 min. The resulting solution was stirred at 0° C. for 10 min, then the cooling bath was removed and the mixture stirred for an additional 10 min before it was finally cooled to −78° C. To this solution of LDA was then added via cannula a −78° C. solution of methyl acetate (6.01 mL, 75.6 mmol) in THF (30 mL) over ˜5 min. This mixture was stirred at −78° C. for 30 min, and then a mixture of chlorotriisopropoxytitanium (27.1 mL, 113 mmol) and THF (30 mL) was added via syringe. After 30 min, a RT solution of (R)-2-methyl-N-(1-(tetrahydro-2H-pyran-4-yl)ethylidene)propane-2-sulfinamide 4 (7.0 g, 30 mmol) in THF (40 mL) was added via cannula over ˜5 min. The reaction was then stirred at −78° C. for 5 h. At that time, while still at −78° C., the reaction was diluted rapidly with water (300 mL) and agitated. The reaction was allowed to gradually warm to RT overnight with stirring. At that time, the mixture was further diluted with EtOAc and water, and the mixture was filtered with copious EtOAc washes. The phases of the filtrate were separated and the aqueous layer was extracted 2× with EtOAc. The organic portions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The crude sample was subjected to column chromatography (ISCO, 330 g silica, 100 mL/min, 0% to 25% i-PrOH/hexanes) to give (S)-methyl 3-((R)-1,1-dimethylethylsulfinamido)-3-(tetrahydro-2H-pyran-4-yl)butanoate 5 (6.5 g, 70%). LCMS (conditions D) for 5: tR=1.90 min, m/e=306.2 (M+H, base), 328.2 (M+Na).

Provenance & Evidence