Diisopropyl Ether → N-methyl-6-((trityl-1H-imidazol-4-yl)carbonyl)-2-naphthamide

HRID 922715Notes

Reaction equation

HRID 922715 reaction equation
[OH:1][CH:2]([C:17]1[N:18]=[CH:19][N:20]([C:22]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:21]=1)[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]([NH:15][CH3:16])=[O:14])[CH:7]=[CH:6]2.CN(C)C(=O)C.C(OC(C)C)(C)C>[O-2].[O-2].[Mn+4].C(OCC)(=O)C>[CH3:16][NH:15][C:13]([C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:2]([C:17]3[N:18]=[CH:19][N:20]([C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[CH:21]=3)=[O:1])[CH:4]=2)[CH:9]=1)=[O:14]

Participants

6

Reactant 3

HCID 7914Diisopropyl EtherHCID 31374DimethylacetamideHCID 574658056-(hydroxy(1-trityl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide

Product 1

HCID 18769037N-methyl-6-((trityl-1H-imidazol-4-yl)carbonyl)-2-naphthamideYield 82.2%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
60 °C

Procedure

6-[Hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (10.0 g, 19.1 mmol) and manganese dioxide (10.0 g, 115.0 mmol) were added to a mixed solvent of N,N-dimethylacetamide (25 mL) and ethyl acetate (63 mL), and the mixture was stirred at 60° C. for 3 hr. The insoluble material was filtered off at the same temperature, and washed with ethyl acetate (60 mL). The filtrate and washing were combined and concentrated to the volume of 30 mL under reduced pressure. To the residue was added dropwise diisopropyl ether (100 mL), and the mixture was stirred at room temperature. The obtained crystals were collected by filtration, and washed with diisopropyl ether (30 mL) to give crude wet crystals (26.4 g). The crude wet crystals (10.8 g) were added to ethyl acetate (54 mL), and the mixture was warmed to 60° C., and stirred for 0.5 hr. The obtained mixture was allowed to cool to room temperature, and diisopropyl ether (108 mL) was added dropwise thereto. The mixture was stirred with cooling to 5° C. The obtained crystals were collected by filtration, and washed with a mixed solvent (27 mL) of diisopropyl ether/ethyl acetate (2:1, volume ratio). The obtained wet crystals were dried under reduced pressure to give N-methyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamide (8.2 g, 15.7 mmol). yield 82%.

Workup

  1. filtrationThe insoluble material was filtered off at the same temperature
  2. washwashed with ethyl acetate (60 mL)
  3. washThe filtrate and washing
  4. concentrationconcentrated to the volume of 30 mL under reduced pressure
  5. additionTo the residue was added dropwise diisopropyl ether (100 mL)
  6. stirringthe mixture was stirred at room temperature
  7. filtrationThe obtained crystals were collected by filtration
  8. washwashed with diisopropyl ether (30 mL)
  9. customto give crude wet crystals (26.4 g)
  10. temperaturethe mixture was warmed to 60° C.
  11. stirringstirred for 0.5 hr
  12. temperatureto cool to room temperature
  13. stirringThe mixture was stirred
  14. temperaturewith cooling to 5° C
  15. filtrationThe obtained crystals were collected by filtration
  16. washwashed with a mixed solvent (27 mL) of diisopropyl ether/ethyl acetate (2:1, volume ratio)
  17. customThe obtained wet crystals were dried under reduced pressure

Sources & evidence

ORD record
ord-4b42b2b8dfbe4e9486cc48f2a4e394b8
Source dataset
uspto-grants-2016_03
Patent number
US09278938B2

Reaction notes

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