Ammonium Chloride → Tert-butyl 3-ethynyl-3-hydroxypyrrolidine-1-carboxylate

Ethynyl magnesium chloride (0.5 M in THF, 210 mL, 105 mmol) was diluted with THF (100 mL) and cooled in an ice-water bath. A solution of N-Boc-3-pyrrolidinone (9.21 g, 50 mmol) (Example 97A above) in THF (100 mL) was added dropwise with cooling. The mixture was stirred for 2 h and aqueous ammonium chloride solution (100 mL, 15% WN) was then added. The mixture was then extracted with ether (2×400 mL). The ether layers were washed with saturated aqueous sodium chloride solution (200 mL), combined, dried (MgSO4), filtered and concentrated. The residue was chromatographed (Biotage Flash 40S, EtOAc—hexanes as solvent) to give rac-N-Boc-3-hydroxy-3-ethynyl-pyrrolidine as a pale yellow oil that crystallized on standing. (Yield 10.13 g, 96.4%).

1. temperaturecooled in an ice-water bath
2. temperaturewith cooling
3. extractionThe mixture was then extracted with ether (2×400 mL)
4. washThe ether layers were washed with saturated aqueous sodium chloride solution (200 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was chromatographed (Biotage Flash 40S, EtOAc—hexanes as solvent)

ORD record

ord-39cbb6bffbc745fca177de117f2f436f

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06252086B1