Hydroxyamine hydrochloride → 6-Methylazepane-2,4-dione

Temperature

0 °C

150 g 5-methylcyclohexane-1,3-dione was dissolved in 1.4 L methanol and 82.5 g hydroxylamine hydrochloride was added. The mixture was stirred for 1.5 h under reflux. The solvent was removed in vacuo and the residue was dissolved in 1 L acetonitrile and was cooled to 0° C. Triethylamine was added followed by addition of a solution of 4-toluenesulfonyl chloride in 1.1 L acetonitrile. The mixture was stirred for 1 h at RT, 6.7 mL of water was added and the mixture was stirred for additional 1 h while gently warming the mixture to 55° C. The volatiles were removed in vacuo. 250 mL water was added to the residue and the pH was adjusted to 5 with 5 N aq. NaOH and the volatiles were removed in vacuo. The solids were extracted with acetone and after concentration in vacuo the residue was purified by column chromatography on silica gel with ethyl acetate to yield 82.6 g of the desired compound.

1. temperatureunder reflux
2. customThe solvent was removed in vacuo
3. dissolutionthe residue was dissolved in 1 L acetonitrile
4. additionTriethylamine was added
5. additionfollowed by addition of a solution of 4-toluenesulfonyl chloride in 1.1 L acetonitrile
6. stirringThe mixture was stirred for 1 h at RT
7. addition6.7 mL of water was added
8. stirringthe mixture was stirred for additional 1 h
9. temperaturewhile gently warming the mixture to 55° C
10. customThe volatiles were removed in vacuo
11. addition250 mL water was added to the residue
12. customthe volatiles were removed in vacuo
13. extractionThe solids were extracted with acetone
14. concentrationafter concentration in vacuo the residue
15. customwas purified by column chromatography on silica gel with ethyl acetate

ORD record

ord-b4061f55435e4671ba33a8b32316c51d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642774B2