Allyl bromide → tert-butyl ((5R,6R)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-tert-butyl (5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (600 mg, 1.397 mmol) in THF (14 ml) was added potassium bis(trimethylsilyl)amide, (1M in THF) (8.38 ml, 8.38 mmol) dropwise at −78° C. and the mixture was stirred for 30 min at −78° C. Neat allyl bromide (0.363 ml, 4.19 mmol) was then added dropwise and the mixture was stirred for 30 min. The reaction mixture was quenched with sat. aq. NH4Cl solution at −78° C., then allowed to reach RT and extracted with ethyl acetate. The organic extracts were washed with brine and concentrated. The residue was separated by silica gel chromatography on a 40 g RediSep Gold column using 10-60% EtOAc/heptane solvent gradient to afford less polar trans-isomer tert-butyl ((5R,6R)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (170 mg, 0.362 mmol, 25.9% yield), and more polar cis-isomer tert-butyl ((5R,6S)-6-allyl-5-(2-fluoro-5-nitrophenyl)-2,2,5-trimethyl-1,1-dioxido-5,6-dihydro-2H-1,4-thiazin-3-yl)carbamate (263 mg, 0.560 mmol).

Provenance & Evidence