Diisopropylethylamine → (3R)-1-(2-Fluoro-4-nitrophenyl)pyrrolidin-3-ol

(3R)-3-Hydroxypyrrolidine hydrochloride (20 g, 0.163 M) was suspended by stirring in acetonitrile (200 ml) under nitrogen at 50°, and treated with N,N-diisopropylethylarnine (52.5 g, 0.41 M) and 3,4-difluoronitrobenzene (25.9 g, 0.153 M). The mixture was heated at 90° for 17 hours, then the solvent evaporated. The residue was dissolved in dichloromethane (500 ml) and washed with 5% aqueous sodium dihydrogen phosphate (300 ml), which caused partial precipitation. The precipitate was filtered, washed, and the combined aqueous layers re-extracted with dichloromethane (200 ml). The organic layers were evaporated, and the residue combined with the previously filtered material, and dried by azeotroping with toluene to give the desired product (35 g), of sufficient quality for use without purification.

1. temperatureThe mixture was heated at 90° for 17 hours
2. customthe solvent evaporated
3. dissolutionThe residue was dissolved in dichloromethane (500 ml)
4. washwashed with 5% aqueous sodium dihydrogen phosphate (300 ml), which
5. customprecipitation
6. filtrationThe precipitate was filtered
7. washwashed
8. extractionthe combined aqueous layers re-extracted with dichloromethane (200 ml)
9. customThe organic layers were evaporated
10. customdried
11. customby azeotroping with toluene

ORD record

ord-02b4b551b33f4279af2c0200913140de

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06617339B1