Trifluoroacetic acid → HCID 67348810, compound

Temperature

0 °C

To a solution of 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (2.5 g, supplier Atlantic Scitech) and DIPEA (5.45 ml, 31.2 mmol) in dry dichloromethane (DCM) (60 ml) at 0° C. under argon was added 4-cyanobenzenesulfonyl chloride (2.64 g, 13.11 mmol) and the resulting clear solution stirred at 0° C. for 2 h. Saturated aqueous NaHCO3 (100 mL) was added, the layers separated, then the organic layers washed with 2M aqueous HCl (100 mL) and passed through a hydrophobic frit. The solution in DCM was cooled to 0° C., then TFA (8.87 ml, 115 mmol) was added. The resulting very pale yellow solution was allowed to warm to room temperature over 1 h, then stirred for 18 h. Aqueous 2M NaOH (100 mL) was added cautiously with cooling (0° C.) and layers were separated. The organic layer was extracted with 1M aqueous HCl (3×30 mL). With cooling (0° C.), the combined acidic aqueous layers were adjusted to pH 7 by addition of solid NaOH, and then extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo to give the title compound as a white solid (2.35 g).

1. customthe layers separated
2. washthe organic layers washed with 2M aqueous HCl (100 mL)
3. temperatureThe solution in DCM was cooled to 0° C.
4. temperatureto warm to room temperature over 1 h
5. stirringstirred for 18 h
6. temperaturewith cooling (0° C.) and layers
7. customwere separated
8. extractionThe organic layer was extracted with 1M aqueous HCl (3×30 mL)
9. temperatureWith cooling (0° C.)
10. additionthe combined acidic aqueous layers were adjusted to pH 7 by addition of solid NaOH
11. extractionextracted with EtOAc (2×50 mL)
12. washThe combined organic layers were washed with brine (30 mL)
13. dry with materialdried (MgSO4)
14. filtrationfiltered
15. concentrationconcentrated in vacuo

ORD record

ord-79acd032093a4f5f8a323c1877b47622

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697703B2