(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid → Quinoxaline

To a solution of N-Boc-trans-4-hydroxy-L-proline 2-11 (2.404 g, 10.396 mmol) in DMF (14 ml) and THF (60 ml) at 0° C. was added t-BuONa (3.0 g, 31.189 mmol) portionwise. The reaction mixture was allowed to warm up to rt. After stirring for 1 h, the mixture was cooled down to 0° C. and 2-chloro-3-(1,1-difluoroallyl)quinoxaline 2-10 (2.45 g, ˜10.396 mmol) was added and warmed up to rt. After stirring for 4 h, the reaction mixture was quenched with 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (3×), and the organic layer was combined, washed with water, brine, dried and concentrated in vacuo. To the residue in DCM (50 ml) and MeOH (10 ml) was added TMSCHN2 (10.4 ml, 20.792 mmol, 2.0 M in Hexane). The solution was stirred at rt for 30 min then concentrated in vacuo. The residue was purified by flash chromatography on CombiFlash with Hexane to 30% ethyl acetate in hexane to afford desired product 1-1 (3.84 g, 82%). MS (ESI): m/z=450.24 [M+H].

1. temperaturethe mixture was cooled down to 0° C.
2. temperaturewarmed up to rt
3. stirringAfter stirring for 4 h
4. customthe reaction mixture was quenched with 1 N HCl at 0° C
5. extractionThe aqueous layer was extracted with EtOAc (3×)
6. washwashed with water, brine
7. customdried
8. concentrationconcentrated in vacuo
9. stirringThe solution was stirred at rt for 30 min
10. concentrationthen concentrated in vacuo
11. customThe residue was purified by flash chromatography on CombiFlash with Hexane to 30% ethyl acetate in hexane

ORD record

ord-b348e6af68bc4f7d86d9695c1bb4c92d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08648037B2