Trimethylsulfonium iodide → HCID 86724400, compound

Participants

Reaction Conditions

Reaction Steps

Into a different flask, trimethylsulfonium iodide (181.35 g, 888.65 mmol) was dissolved in THF. The solution was cooled to −30° C. Lithium hexamethyldisilazide (888.65 mL, 1 M solution in THF, 888.65 mmol) was added over 25 mins. The internal temperature went from −30° C. to −26° C. upon the addition. The reaction was stirred at −30° C. for 30 mins. To this solution was added the (S)-2-(fluoromethyl)oxirane solution (that was prepared in the previous flask). The addition was done over 5 mins at −30° C. The reaction was then allowed to warm up to RT and stirred for 3 h. It was then cooled to 3° C. (internal temperature) using an ice bath and 1-methyl-2-pyrrolidinone (100 mL) was added. The internal temperature rose to 8° C. tert-Butyl bromoacetate (131.22 mL, 888.65 mmol) in 1-methyl-2-pyrrolidinone (100 mL) was added dropwise using a dropping funnel and ensuring the temperature remained between 17-20° C. The reaction was stirred in the ice bath for 10 mins until the temperature went to 5° C. The ice bath was removed and it was stirred at RT overnight. Water (2 L) was poured into the reaction mixture and followed by Et2O (1 L). After stirring for 10 mins the two layers were separated and the aqueous layer was extracted with Et2O (4×500 mL). The combined organic extracts were dried over MgSO4 and concentrated. The crude product was purified by silica gel column chromatography using hexanes initially and then 5% EtOAc in hexanes to obtain the title compound as a yellow liquid (57 g, 63%).

Provenance & Evidence