Dimethylacetamide → 1-(6-Nitro-pyridin-3-yl)-azetidin-3-ol

Participants

Reaction Conditions

Reaction Steps

A 500-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was purged with nitrogen and charged with 2-nitro-5-bromopyridine (3.00 g, 14.8 mmol), 3-hydroxyazetidine hrdrochloride (2.91 g, 26.56 mmol), N,N-diisopropylethyl amine (5.67 g, 43.91 mmol) and tetrabutylammonium iodide (8.17 g, 22.1 mmol) and N,N-dimethylacetamide (15 mL). This mixture was heated at 120° C. (bath temperature) for 14 h. After this time, the reaction mixture was cooled to room temperature, diluted with water (100 mL) and extracted with ethyl acetate (4×100 mL). The combined organic layers were washed with brine (250 mL) and dried over sodium sulfate. The drying agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was purified using a silica gel column, eluting the desired product with 80% ethyl acetate in hexanes to afford a 49% yield (1.43 g) of 120a as a yellow semi-solid: 1H NMR (500 MHz, DMSO-d6) δ 8.13 (d, 1H, J=9.0 Hz), 7.70 (d, 1H, J=2.5 Hz), 6.91 (m, 1H), 5.83 (d, 1H, J=6.0 Hz), 4.65 (m, 1H), 4.31 (m, 2H), 3.83 (m, 2H); MS (ESI+) m/z 196.2 (M+H).

Provenance & Evidence