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

Temperature

120 °C

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).

1. customA 500-mL single-neck round-bottomed flask equipped with a magnetic stirrer
2. temperaturereflux condenser
3. customwas purged with nitrogen
4. temperatureAfter this time, the reaction mixture was cooled to room temperature
5. extractionextracted with ethyl acetate (4×100 mL)
6. washThe combined organic layers were washed with brine (250 mL)
7. dry with materialdried over sodium sulfate
8. customThe drying agent was removed by filtration
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe resulting residue was purified
11. washeluting the desired product with 80% ethyl acetate in hexanes

ORD record

ord-4c9d8d80d3a84293aa4f1b61a88d42e9

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249123B2