Methyl iodide → (3-Methoxy-4-(2-methoxypropan-2-yl)phenyl)(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4'-piperidine]-1'-yl)methanone

Participants

Reaction Steps

(4-(2-Hydroxypropan-2-yl)-3-methoxyphenyl)(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)methanone (crude material from step 1) was dissolved in a mixture of THF (3 mL) and DMF (3 mL). NaH (28 mg, 0.69 mmol) was added and the reaction mixture was allowed to stir for 2 minutes. MeI (54 μL, 0.86 mmol) was then added and the reaction mixture was allowed to stir for 1 h. The reaction mixture was evaporated to dryness and the residue was suspended in 25 mL of dichloromethane. The suspension was washed two times with a 1M solution of hydrochloric acid, followed by two washes with a saturated aqueous solution of sodium bicarbonate, followed by two washes of a saturated aqueous solution of sodium chloride. The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness to yield the crude product. The crude material was purified by column chromatography utilizing a gradient of 0-35% ethyl acetate in hexanes give (3-methoxy-4-(2-methoxypropan-2-yl)phenyl)(spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)methanone (94 mg, 35% over 2 steps). ESI-MS m/z calc. 446.2, found 447.5 (M+1)+; Retention time: 7.60 minutes (15 min run). 1H NMR (400 MHz, DMSO) δ 7.68-7.65 (m, 1H), 7.50-7.49 (m, 1H), 7.40 (d, J=7.9 Hz, 1H), 7.17-6.98 (m, 5H), 6.29-6.28 (m, 1H), 6.18-6.17 (m, 1H), 4.49-4.34 (m, 1H), 3.83 (s, 3H), 3.80-3.41 (m, 3H), 3.13 (s, 3H), 2.11-1.81 (m, 4H) and 1.50 (s, 6H).

Provenance & Evidence