Acetic Anhydride → HCID 67468474, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 7-chloro-1′-(3-methoxy-4-(trifluoromethyl)benzoyl)spiro-[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbaldehyde (310 mg, 0.61 mmol) in ethanol (1.5 mL) was added an aqueous solution of hydroxylamine hydrochloride (190 mg, 2.7 mmol) and sodium acetate (380 mg, 4.6 mmol) in water (1.5 mL). The mixture was heated at 95° C. for 2 hours. The reaction mixture was cooled to 25° C., water was added and the white precipitate that formed was collected by filtration, washed thoroughly with water and dried by azeotrope with toluene. The solid was dissolved in Ac2O (1.1 mL, 12 mmol) and was heated at 140° C. for 3.5 hours. The mixture was cooled to 25° C., poured into ice, diluted with dichloromethane (30 mL), and neutralized with NaHCO3 (2 g). The organic phase was separated, and the aqueous phase further extracted twice with dichloromethane. The organic layers were combined, washed with brine, dried, filtered, concentrated to a yellow oil that was purified by column chromatography (silica gel, 5-30% AcOEt in hexanes) to yield 7-chloro-1′-(3-methoxy-4-(trifluoromethyl)benzoyl)spiro[benzo-[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbonitrile. 1H NMR (400 MHz, CDCl3) δ 8.06 (t, J=10.1 Hz, 1H), 7.70 (s, 1H), 7.64 (dd, J=8.6, 1.6 Hz, 1H), 7.17 (d, J=2.2 Hz, 1H), 7.10 (dd, J=8.7, 2.2 Hz, 1H), 7.03 (dd, J=10.4, 6.3 Hz, 2H), 6.13 (d, J=4.0 Hz, 1H), 4.61 (s, 1H), 3.96 (d, J=20.2 Hz, 3H), 3.89-3.06 (m, 3H), 2.16-1.81 (m, 4H). ESI-MS m/z calc. 501.9. found 502.0 (M+1)+; Retention time: 2.17 minutes (3 min run). 1′-(4-Isopropoxy-3-methylbenzoyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-9-carbonitrile was synthesized from 1′-(4-isopropoxy-3-methylbenzoyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-9-carbaldehyde using the procedure described above.

Provenance & Evidence