Aminopyrazine → (2S,4R)-tert-Butyl 4-fluoro-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylate

To a solution of aminopyrazine (3.85 g, 40.5 mmol) in THF (120 mL) was added isopropylmagnesium chloride (2.0 M THF solution, 19 mL, 38 mmol) dropwise at 0° C. The resulting slurry was stirred at room temperature for 30 min. A solution of commercially available (2S,4R)-1-tert-butyl 2-methyl 4-fluoropyrrolidine-1,2-dicarboxylate (3.2 g, 12.9 mmol) in THF (10 mL) was added to the slurry. The reaction mixture was stirred at room temperature for 4 h and quenched with methanol (3 mL). After concentration in vacuo, ethyl acetate (120 mL) and 1N HCl (60 mL) were added to the residue. The organic layers were washed with 1N HCl, water, brine, and dried over Na2SO4, and filtered. Concentration gave (2S,4R)-tert-butyl 4-fluoro-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylate 65A (4.1 g, 100%) as a colorless foam. LC/MS [M+H]+: 311; Ret time (Method F): 1.46 min.

1. stirringThe reaction mixture was stirred at room temperature for 4 h
2. customquenched with methanol (3 mL)
3. concentrationAfter concentration in vacuo, ethyl acetate (120 mL) and 1N HCl (60 mL)
4. additionwere added to the residue
5. washThe organic layers were washed with 1N HCl, water, brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationConcentration

ORD record

ord-32e01abce06144ad8a3f990e6c0f1aab

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415340B2