Methylhydrazine → Tert-butyl 3-(aminooxy)pyrrolidine-1-carboxylate

HRID 1821817Notes

Reaction equation

HRID 1821817 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[O:12][CH:13]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]1.CNN>C(Cl)Cl.CO>[NH2:3][O:12][CH:13]1[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14]1

Participants

5

Reactant 2

HCID 6061MethylhydrazineHCID 19691445tert-butyl 3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)oxy]pyrrolidine-1-carboxylate

Product 1

HCID 19691331Tert-butyl 3-(aminooxy)pyrrolidine-1-carboxylateYield 77.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To an ice-cold solution of tert-butyl 3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)oxy]pyrrolidine-1-carboxylate (0.96 g, 2.8 mmol) in CH2Cl2 (16 mL) and MeOH (4 mL) was added methylhydrazine (0.70 mL, 13 mmol) dropwise. The stirred reaction mixture was allowed to slowly warm to ambient temperature. After 2 h, the reaction mixture was concentrated under reduced pressure. To the residue was added CH2Cl2 (20 mL) and with the aid of sonication a solid formed and was collected by vacuum filtration. The filtrate was concentrated and purified by column chromatography (silica gel, 75:25 hexanes/EtOAc to 25:75 hexanes/EtOAc) to afford tert-butyl 3-(aminooxy)pyrrolidine-1-carboxylate (440 mg, 76%): 1H NMR (500 MHz, CDCl3) δ 1.46 (9H, s), 1.82-1.98 (1H, m), 2.04-2.10 (1H, m), 3.31-3.65 (4H, m), 4.24-4.27 (1H, m), 5.37.

Workup

  1. customThe stirred reaction mixture
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. additionTo the residue was added CH2Cl2 (20 mL)
  4. customwith the aid of sonication a solid
  5. customformed
  6. filtrationwas collected by vacuum filtration
  7. concentrationThe filtrate was concentrated
  8. custompurified by column chromatography (silica gel, 75:25 hexanes/EtOAc to 25:75 hexanes/EtOAc)

Sources & evidence

ORD record
ord-9e02d667f66a420995ec24c603a5c40c
Source dataset
uspto-grants-2009_10
Patent number
US07608627B2

Reaction notes

Loading…