Isopropyl iodide → HCID 68845071, compound

To a stirred suspension of 2-hydroxymethyl-5-methoxy-4-pyridone (1.00 g, 6.45 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (60% dispersion in mineral oil; 0.26 g, 6.5 mmol). The fizzy mixture was stirred for 5-10 minutes before adding, dropwise, 2-iodopropane (0.65 mL, 6.5 mmol). The reaction was stirred at room temperature overnight and then at reflux for 4 hours. At this time, additional sodium hydride (0.07 g, 1.8 mmol) and 2-iodopropane (0.16 mL, 1.6 mmol) were added and the mixture was heated at reflux for another 4 hours. The reaction was then concentrated and partitioned between methylene chloride and aqueous sodium carbonate solution. The resulting biphasic mixture was filtered through Celite to remove a small amount undissolved solid. The organic layer of the filtrate was dried (sodium sulfate) and concentrated to afford a dark brown oil. This material was purified by flash chromatography over silica (methylene chloride/methanol) to afford 410 g (32%) of product as a crystalline light brown solid: 1H NMR (CDCl3) δ 7.92 (s, 1H), 6.61 (s, 1H), 4.54 (sept, J=6.2 Hz, 1H), 4.53 (s, 2H), 3.79 (s, 3H), 1.29 (d, J=6.0 Hz, 6H) ppm.

1. additionbefore adding
2. stirringThe reaction was stirred at room temperature overnight
3. temperatureat reflux for 4 hours
4. temperaturethe mixture was heated
5. temperatureat reflux for another 4 hours
6. concentrationThe reaction was then concentrated
7. custompartitioned between methylene chloride and aqueous sodium carbonate solution
8. filtrationThe resulting biphasic mixture was filtered through Celite
9. customto remove a small amount undissolved solid
10. dry with materialThe organic layer of the filtrate was dried (sodium sulfate)
11. concentrationconcentrated
12. customto afford a dark brown oil
13. customThis material was purified by flash chromatography over silica (methylene chloride/methanol)

ORD record

ord-915af2ad94ce48a8a47fe5218e49128c

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07541466B2