Acetic Anhydride → HCID 86660257, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3′-methyl-1-(2,2,2-trifluoroacetyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-carbaldehyde (25 mg, 0.07 mmol) in ethanol (125 μL) at 60° C. was added an aqueous solution of hydroxylamine hydrochloride (20.7 mg, 0.30 mmol) and sodium acetate (41.2 mg, 0.50 mmol) in water (125.0 μL). The solution was stirred at 60° C. for 2 hours. The reaction was cooled to 25° C., water added and the precipitate that formed was collected by filtration. The solids were washed thoroughly with water and dried under vacuum, dissolved in Ac2O (119.1 μL, 1.26 mmol) and heated at 140° C. for 5 h. The reaction was cooled to 25° C., poured onto ice, basified by addition of solid NaHCO3 until no more foaming occurred and extracted with dichloromethane (3×5 mL). The organic phases were combined, dried, filtered and concentrated to yield a residue that was purified by silica gel chromatography using a gradient of 0.5-45% EtOAc in hexanes to yield 3-methyl-1′-(2,2,2-trifluoroacetyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbonitrile (10 mg, 40%). ESI-MS m/z calc. 375.1, found 376.3 (M+1)+; Retention time 2.01 minutes (3 min run).

Provenance & Evidence