2-Acetyl-5-chlorothiophene → (NE)-N-[1-(5-chlorothiophen-2-yl)ethylidene]hydroxylamine

Combined 1-(5-chlorothiophen-2-yl)ethanone (100 g, 622 mmol), hydroxylamine hydrochloride (47.6 g, 685 mmol, 1.1 eq) and sodium acetate (56.2 g, 685 mmol, 1.1 eq) in 1 L of ethanol and 300 mL of water. The reaction was heated to reflux. After 3 h, the reaction was cooled to rt and concentrated. The residue was slurried in 500 mL of water overnight, filtered and dried to afford the crude solid. Purified by extraction of the solid with hot dichloromethane, cooling to rt and filtering to remove unreacted starting material. The solid was slurried in hot dichloromethane several times to extract the solid enriched in the first eluting (E-oxime) compound (100% DCM) after concentration. The highly crystalline material was purified by column chromatography using 100% dichloromethane to afford (E)-1-(5-chlorothiophen-2-yl)ethanone oxime. NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H), 7.21 (d, J=3.9 Hz, 1H), 7.07 (d, J=3.9 Hz, 1H), 2.12 (s, 3H) ppm.

1. temperatureThe reaction was heated to reflux
2. concentrationconcentrated
3. waitThe residue was slurried in 500 mL of water overnight
4. filtrationfiltered
5. customdried
6. customto afford the crude solid
7. customPurified by extraction of the solid with hot dichloromethane
8. temperaturecooling to rt
9. filtrationfiltering
10. customto remove unreacted
11. extractionto extract the solid
12. washfirst eluting (E-oxime) compound (100% DCM)
13. concentrationafter concentration
14. customThe highly crystalline material was purified by column chromatography

ORD record

ord-3de2de1ef60f47eea71596b36d6ac44e

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759371B2