Allyl bromide → HCID 86728116, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-tert-butyl (5-(5-bromo-2-fluoropyridin-3-yl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (1.02 g, 2.197 mmol) in THF (13 mL) at −78° C. was added potassium bis(trimethylsilyl)amide (1 M in THF, 13.2 mL, 13.2 mmol) dropwise. The solution was stirred at −78° C. for 30 min and allyl bromide (0.570 mL, 6.59 mmol) was added. The reaction mixture was stirred at −78° C. for 70 min, quenched with saturated NH4Cl, warmed to room temperature and diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (2×). The combined organic extracts were washed with brine (1×), dried over MgSO4, filtered, concentrated. Purification by flash column chromatography on silica gel (40 g, 10% to 40% EtOAc in hexanes) gave tert-butyl ((5R,6R)-6-allyl-5-(5-bromo-2-fluoropyridin-3-yl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (0.703 g, 1.39 mmol, 63% yield) as a white solid, LC/MS (ESI+) m/z=504 (M+H); and tert-butyl ((5R,6S)-6-allyl-5-(5-bromo-2-fluoropyridin-3-yl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (0.280 g, 0.555 mmol, 25% yield) as white solid, LC/MS (ESI+) m/z=504 (M+H). The two products were recombined and used in the next step.

Provenance & Evidence