Trifluoroacetic acid → 6,6-Dimethylpiperazin-2-one

A mixture of (2-tert-butoxycarbonylamino-2-methyl-propylamino)-acetic acid methyl ester (compound N; 26.5 g) in DCM (800 mL) was stirred at ambient temperature, TFA (180 mL) was added drop-wise. The mixture was stirred at 30-40° C. for 5 h before it was concentrated in vacuo. The residue was partitioned between dissolved toluene and water. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residual solid was dissolved in a mixture of ethanol (400 mL) and methanol (90 mL). K2CO3 (207 g) was added and the mixture was refluxed overnight. The mixture was cooled to room temperature. DCM (2500 mL) was added, and the mixture was stirred for 1 hour at ambient temperature. The solid was filtered off, and the filtrate was concentrated in vacuo to afford 6,6-dimethyl-piperazin-2-one (Compound I; 5.85 g) as a white solid sufficiently pure for the next step.

1. stirringThe mixture was stirred at 30-40° C. for 5 h before it
2. concentrationwas concentrated in vacuo
3. customThe residue was partitioned
4. dissolutionbetween dissolved toluene and water
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. dissolutionThe residual solid was dissolved in a mixture of ethanol (400 mL) and methanol (90 mL)
9. additionK2CO3 (207 g) was added
10. temperaturethe mixture was refluxed overnight
11. temperatureThe mixture was cooled to room temperature
12. additionDCM (2500 mL) was added
13. stirringthe mixture was stirred for 1 hour at ambient temperature
14. filtrationThe solid was filtered off
15. concentrationthe filtrate was concentrated in vacuo

ORD record

ord-869ab05564744c0590b9ac25902086ad

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216961B2