Hexahydro-1,4-diazepine → 1-[(6-Chloropyridin-3-yl)carbonyl]-1,4-diazepane

Temperature

0 °C

A solution of homopiperazine (12.5 g, 125 mmol) and ethyl-6-chloronicotinate (9.28 g, 50 mmol) in THF (150 mL) was cooled to 0° C. and LiOEt (1 M in THF, 50 mL, 50 mmol) was then added over 20 minutes. The resulting mixture was stirred at 0° C. for 2 h, then warmed to 20° C. and held at this temperature for 17 h. The resulting mixture was then treated with 162 mL of an aqueous solution containing 1.53 g of NaOAc and 8.2 mL of acetic acid. The resulting layers were separated and the organic was diluted with hexane (50 mL) and extracted again with the same aqueous solution as utilized above. The aqueous pH was then increased to 10 through addition of 50% NaOH(aq) (15 mL). After extraction with dichloromethane (3×250 mL) the combined organics were dried over sodium sulfate, filtered, and concentrated to yield the title compound as an oil.

1. temperaturewarmed to 20° C.
2. waitheld at this temperature for 17 h
3. customThe resulting layers were separated
4. additionthe organic was diluted with hexane (50 mL)
5. extractionextracted again with the same aqueous solution
6. temperatureThe aqueous pH was then increased to 10 through addition of 50% NaOH(aq) (15 mL)
7. extractionAfter extraction with dichloromethane (3×250 mL) the combined
8. dry with materialorganics were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-adbeb4197c364825838568929c581689

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08748596B2