Trifluoroacetic acid → Tert-butyl 2'-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-carboxylate

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Reaction Steps

Trifluoroacetic acid (443 pt, 5.75 mmol) was added to a solution of 2-pyrrol-1-ylphenol (457 mg, 2.87 mmol) and tert-butyl 2-methyl-4-oxo-piperidine-1-carboxylate (613 mg, 2.87 mmol) in dichloromethane (19 mL) and the solution was vigorously stirred for 16 h. The reaction mixture was quenched with saturated aqueous NaHCO3, and the organics were extracted with EtOAc (3×200 mL). The combined organics were washed with water, brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (silica gel: 0-10% EtOAc in dichloromethane) to give tert-butyl 2′-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-carboxylate as a brown oil. The crude residue was dissolved in a solution of HCl in dioxane (1.4 mL of 4.0 M, 5.6 mmol) and stirred for 30 min at room temperature. The volatiles were removed in vacuo and the residue was dissolved in diethylether. The solids were collected by filtration to provide 2′-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine] hydrochloride (386 mg, 46%) as a reddish brown solid. ESI-MS m/z calc. 254.1, found 255.5 (M+1)+; Retention time: 1.12 minutes (3 min run).

Provenance & Evidence