Dimethylformamide → tert-Butyl[(1S)-7-oxo-1-(5-phenyl-1H-imidazol-2-yl)octyl]carbamate

HRID 251722Notes

Reaction equation

HRID 251722 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18](=[O:20])[CH3:19])[C:10](O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].BrC[C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=O.C([O-])(=O)C.[NH4+:41].C[N:43]([CH:45]=O)C>CCO.C1(C)C(C)=CC=CC=1.CCOC(C)=O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:10]1[NH:41][C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:45][N:43]=1)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18](=[O:20])[CH3:19])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 6259Phenacyl bromideHCID 10796Cesium carbonateHCID 517165Ammonium AcetateHCID 86627946(2S)-2-[(tert-Butoxycarbonyl)amino]-8-oxononanoic acid

Product 1

HCID 91226371tert-Butyl[(1S)-7-oxo-1-(5-phenyl-1H-imidazol-2-yl)octyl]carbamate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of A1 (1 eq.) and Cs2CO3 (0.5 eq) in EtOH was stirred for 30 min at RT and then concentrated under reduced pressure. 2-Bromoacetophenone (1 eq.) was added to the resulting salt in DMF and the mixture was stirred for 1 h at RT under N2. The DMF was removed by azeotroping with xylene. EtOAc was added, the mixture was filtered and the residue was washed with EtOAc. The combined filtrates were concentrated under reduced pressure. A solution of the resulting oil and ammonium acetate (20 eq.) in xylene was heated at reflux (150° C. bath temperature) for 3 h. The mixture was cooled to RT, diluted with EtOAc and washed with water (×2), sat. aq. NaHCO3 solution and brine. The solution was dried (Na2SO4), concentrated under reduced pressure and the resulting brown oil was purified by chromatography on silica gel eluting with EtOAc/petrol ether (1.5:1) to obtain the imidazole A2 as a colourless oil. 1H NMR (300 MHz, CDCl3) δ: 10.50-9.60 (1H, m), 7.82-7.40 (2H, m), 7.38-7.29 (2H, m), 7.22-7.15 (2H, m), 5.13 (1H, br. s), 4.68-4.55 (1H, m), 2.39 (2H, t, J=7.2 Hz), 2.22-2.06 (4H, m), 1.99-1.80 (1H, m), 1.60-1.50 (2H, m), 1.43 (9H, s), 1.40-1.27 (4H, m). MS (ES) C22H31N3O3 requires: 385, found: 386 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe DMF was removed
  3. customby azeotroping with xylene
  4. additionEtOAc was added
  5. filtrationthe mixture was filtered
  6. washthe residue was washed with EtOAc
  7. concentrationThe combined filtrates were concentrated under reduced pressure
  8. temperatureat reflux (150° C. bath temperature) for 3 h
  9. temperatureThe mixture was cooled to RT
  10. washwashed with water (×2), sat. aq. NaHCO3 solution and brine
  11. dry with materialThe solution was dried (Na2SO4)
  12. concentrationconcentrated under reduced pressure
  13. customthe resulting brown oil was purified by chromatography on silica gel eluting with EtOAc/petrol ether (1.5:1)

Sources & evidence

ORD record
ord-123c4712c1a24857b6007f5a99c6645b
Source dataset
uspto-grants-2011_01
Patent number
US07863294B2

Reaction notes

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