Acetic Anhydride → HCID 60128267, compound

HRID 2307402Notes

Reaction equation

HRID 2307402 reaction equation
[NH2:1][C:2]1[C:3]([CH3:22])=[C:4]([CH:19]=[CH:20][CH:21]=1)[O:5][CH2:6][C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C([O-])(=O)C.[K+].C(OC(=O)C)(=O)C.C(O[N:41]=O)CC(C)C>C1C=CC=CC=1>[NH:1]1[C:2]2[C:3](=[C:4]([O:5][CH2:6][C@@H:7]3[CH2:11][CH2:10][CH2:9][N:8]3[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:19]=[CH:20][CH:21]=2)[CH:22]=[N:41]1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 12132434HCID 12132434, compound

Product 1

HCID 60128267HCID 60128267, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution of t-butyl (2S)-2-[(3-amino-2-methylphenoxy) methyl]pyrrolidine-1-carboxylate (5.00 g, 16.33 mmol), potassium acetate (1.92 g, 19.6 mmol) and acetic anhydride (4.9 mL, 52.3 mmol) in benzene is treated dropwise with isoamylnitrite (4.3 mL, 32.7 mmol), heated at reflux temperature overnight, cooled to room temperature and filtered. The filtercake is washed with benzene. The filtrates are combined and concentrated in vacuo to give a yellow oil residue. The residue is purified by chromatography (silica gel, EtOAc:hexanes, 15:85). The purified oil (5.05 g) is dissolved in ethanol, treated with 40% aqueous NaOH, heated at reflux temperature for 45 min, cooled in an ice-water bath, neutralized to pH 8 with concentrated HCl and concentrated in vacuo to remove the ethanol. The resultant aqueous residue is extracted with EtOAc. The combined extracts are washed sequentially with water and brine, dried over MgSO4 and concentrated in vacuo to give a yellow oil. This oil is purified by chromatography (silica gel, EtOAc:hexanes, 30:70) to give the title product as an off-white solid, 3.52 g, mp 125° 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. concentrationconcentrated in vacuo
  6. customto give a yellow oil residue
  7. customThe residue is purified by chromatography (silica gel, EtOAc:hexanes, 15:85)
  8. dissolutionThe purified oil (5.05 g) is dissolved in ethanol
  9. additiontreated with 40% aqueous NaOH
  10. temperatureheated
  11. temperatureat reflux temperature for 45 min
  12. temperaturecooled in an ice-water bath
  13. concentrationconcentrated in vacuo
  14. customto remove the ethanol
  15. extractionThe resultant aqueous residue is extracted with EtOAc
  16. washThe combined extracts are washed sequentially with water and brine
  17. dry with materialdried over MgSO4
  18. concentrationconcentrated in vacuo
  19. customto give a yellow oil
  20. customThis oil is purified by chromatography (silica gel, EtOAc:hexanes, 30:70)

Sources & evidence

ORD record
ord-2c24944ff77940578c073c1a3ea6381c
Source dataset
uspto-grants-2004_12
Patent number
US06831094B2

Reaction notes

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