Trifluoroacetic acid → 9′-Methylspiro[piperidine-4,4′-[4H]pyrrolo[2,1-c][1,4]benzoxazine]

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-methyl-2-(1H-pyrrol-1-yl)phenol (2.9 g, 16.6 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (3.6 g, 18.2 mmol) in dry dichloromethane (57.4 mL) was added TFA (2.5 mL, 33.1 mmol) over a 15 minutes period and the reaction was stirred at 25° C. for 12 hours. Another portion of TFA (2.5 mL, 33.1 mmol) was added at 25° C. and the reaction was stirred for 2 hours after which time a third portion of TFA (2.55 mL, 33.1 mmol) was added and the mixture was stirred at 25° C. for an additional 12 hours. The reaction mixture was diluted with CH2Cl2 (350 ml) and washed with 1M NaOH (50 ml). The organic phase was dried with MgSO4, filtered, evaporated to dryness and the resulting residue was purified by silica gel chromatography eluting with 0.5-40% MeOH in CH2Cl2 to yield 9-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine] (2.0 g, 48%) obtained as a yellow oil. ESI-MS m/z calc. 254.1, found 255.3 (M+1)+. Retention time: 1.08 minutes (3 min run).

Provenance & Evidence