Triethylamine → HCID 68688740, compound

Participants

Reaction Steps

To a 0° C. solution of phenylmethyl [(3,4-dihydro-1,1-dioxido-7-(trifluoromethyl)-2H-1,2-benzothiazin-3-yl)methyl](2-hydroxyethyl)carbamate (400 mg, 0.873 mmol) in dichloromethane (20 mL, dried by passage through Act I neutral alumina) was added triethylamine (0.243 mL, 1.74 mmol) and methanesulfonic anhydride (228 mg, 1.31 mmol). After 3 h, an additional 70-mg portion of methanesulfonic anhydride was added. After an additional 1 h, a 228-mg portion of methanesulfonic anhydride and a 0.243-mL portion of triethylamine were added. After 10 min, the reaction was diluted with dichloromethane (20 mL), washed with saturated sodium bicarbonate (10 mL), dried (sodium sulfate) and concentrated in vacuo. To a 0° C. solution of this residue in tetrahydrofuran (10 mL) was added, dropwise, lithium bis(trimethylsilyl)amide (1 N in tetrahydrofuran, 1.10 mL, 1.10 mmol). After 20 min, an additional 0.15-mL portion of lithium bis(trimethylsilyl)amide was added dropwise to produce an orange solution. The reaction was diluted with saturated sodium chloride (20 mL). The aqueous layer was extracted with dichloromethane (2×20 mL). The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The residue was purified by chromatography (silica, 10% ethyl acetate/hexanes to ethyl acetate gradient) to provide phenylmethyl 3,4,11,11a-tetrahydro-8-(trifluoromethyl)pyrazino[1,2-b][1,2]benzothiazine-2(1H)-carboxylate 6,6-dioxide (321 mg, 83%) as a white foam. LCMS (neg. ion spectrum) m/z 439.

Provenance & Evidence