Diisopropylamine → HCID 57982420, compound

Temperature

0 °C

To a solution of diisopropylamine (4.42 mL, 31.59 mmol) in THF (20 mL) at 0° C. under Ar, was added n-BuLi (12.63 mL, 31.59 mmol, 2.5 M solution in hexane). The mixture was stirred at 0° C. for 30 min. After cooling to −78° C., (4-chloro-2-fluoro-phenyl)-trimethylsilanyloxyacetonitrile (8.12 g, 31.59 mmol) was added. After stirring at −78° C. for 1.5 h, 1-acetyl-piperidin-4-one (4.45 g, 31.59 mmol) was added. The final mixture was stirred at −20° C. for overnight. After concentration, EtOAc (100 mL) was added. The organic phase was washed with Sat. NH4OAc solution, Sat. NaHCO3 solution and concentrated. The residue was dissolved in MeOH (30 mL). 1N HCl solution (20 mL) was added. The mixture was stirred at RT for 2 h. After concentrating the mixture, EtOAc (50 mL) was added. The organic layer was basified with Sat. NaHCO3, dried over Na2SO4 and concentrated. The residue was purified by column chromatography (Ethyl acetate) to give the desired product (4 g, 42% yield) as a white solid. MS: (ESI), M/Z, 300 (M+1). Retention time: 0.87 min (FA-standard).

1. temperatureAfter cooling to −78° C.
2. stirringAfter stirring at −78° C. for 1.5 h
3. concentrationAfter concentration, EtOAc (100 mL)
4. additionwas added
5. washThe organic phase was washed with Sat. NH4OAc solution, Sat. NaHCO3 solution
6. concentrationconcentrated
7. dissolutionThe residue was dissolved in MeOH (30 mL)
8. addition1N HCl solution (20 mL) was added
9. stirringThe mixture was stirred at RT for 2 h
10. concentrationAfter concentrating the mixture, EtOAc (50 mL)
11. additionwas added
12. dry with materialdried over Na2SO4
13. concentrationconcentrated
14. customThe residue was purified by column chromatography (Ethyl acetate)

ORD record

ord-526aa56aba43400ebea974b8b08f2b67

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399455B2