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

HRID 366728Notes

Reaction equation

HRID 366728 reaction equation
[C:1]([Mg]Cl)#[CH:2].[C:5]([N:12]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13]1)([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Cl-].[NH4+]>C1COCC1>[C:5]([N:12]1[CH2:16][CH2:15][C:14]([OH:17])([C:1]#[CH:2])[CH2:13]1)([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 178462451HCID 178462451, compound

Product 1

HCID 18366064Tert-butyl 3-ethynyl-3-hydroxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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% W/V) 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%).

Workup

  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)

Sources & evidence

ORD record
ord-c89c67dea17243f88b53f8e6642c0243
Source dataset
uspto-grants-2000_10
Patent number
US06130239

Reaction notes

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