Acetic Anhydride → HCID 22643434, compound

HRID 2414776Notes

Reaction equation

HRID 2414776 reaction equation
[NH2:1][C:2]1[C:3]([CH3:21])=[C:4]([CH:18]=[CH:19][CH:20]=1)[O:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7]1.C([O-])(=O)C.[K+].C(OC(=O)C)(=O)C.C(O[N:40]=O)CC(C)C>C1C=CC=CC=1>[NH:1]1[C:2]2[C:3](=[C:4]([O:5][CH:6]3[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:7]3)[CH:18]=[CH:19][CH:20]=2)[CH:21]=[N:40]1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 22643441HCID 22643441, compound

Product 1

HCID 22643434HCID 22643434, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution of t-butyl 3-(3-amino-2-methylphenoxy)pyrrolidin-1-Carboxylate (4.6 g, 15.4 mmol), potassium acetate (1.81 g, 18.5 mmol) and acetic anhydride (5.02 g, 49.2 mmol) in benzene is treated dropwise with isoamylnitrite (4.13 ml, 30.8 mmol), heated at reflux temperature overnight, cooled to room temperature and filtered. The filtercake is washed with benzene. The combined filtrates are concentrated to give a yellow oil residue. The residue is purified by chromatography (SiO2, 25% EtOAc in hexanes). The resultant oil is dissolved in ethanol, treated with 40% aqueous NaOH, heated at reflux temperature for 45 min, cooled with an ice-water bath, neutralized to pH 9 with concentrated HCl and concentrated in vacuo. The resulting aqueous mixture is extracted with EtOAc. The combined extracts are washed with water and brine, dried over MgSO4 and concentrated in vacuo to give the title compound as a tan solid, 2.6 g, mp 196-198° C., identified by NMR and mass spectral analyses.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature overnight
  3. filtrationfiltered
  4. washThe filtercake is washed with benzene
  5. concentrationThe combined filtrates are concentrated
  6. customto give a yellow oil residue
  7. customThe residue is purified by chromatography (SiO2, 25% EtOAc in hexanes)
  8. dissolutionThe resultant oil is dissolved in ethanol
  9. additiontreated with 40% aqueous NaOH
  10. temperatureheated
  11. temperatureat reflux temperature for 45 min
  12. temperaturecooled with an ice-water bath
  13. concentrationconcentrated in vacuo
  14. extractionThe resulting aqueous mixture is extracted with EtOAc
  15. washThe combined extracts are washed with water and brine
  16. dry with materialdried over MgSO4
  17. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9ef75526f16f444f98f791e9d5606414
Source dataset
uspto-grants-2004_11
Patent number
US06815456B2

Reaction notes

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