1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 178453377, compound

HRID 1913513Notes

Reaction equation

HRID 1913513 reaction equation
N12CCCN=C1CCCCC2.[Cl-].[Li+].C(N1C=C(C=O)N=C1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[C:40]([O:44][C:45]([NH:47][CH2:48][CH2:49][CH2:50]/[C:51](=[CH:59]\[C:60]1[N:61]=[CH:62][N:63](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:64]=1)/[C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])=[O:46])([CH3:43])([CH3:42])[CH3:41].C(OC(NCCC/C(=C/C1N=CN(C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=1)/C(OC(C)(C)C)=O)=O)(C)(C)C>C(#N)C.CO.[C].[Pd]>[C:40]([O:44][C:45]([NH:47][CH2:48][CH2:49][CH2:50][CH:51]([CH2:59][C:60]1[N:61]=[CH:62][NH:63][CH:64]=1)[C:52]([O:54][C:55]([CH3:56])([CH3:57])[CH3:58])=[O:53])=[O:46])([CH3:41])([CH3:42])[CH3:43]

Participants

9

Reactant 5

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 433294Lithium ChlorideHCID 6182331-(triphenylmethyl)-1H-imidazole-4-carbaldehydeHCID 86675822HCID 86675822, compoundHCID 86675823HCID 86675823, compound

Product 1

HCID 178453377HCID 178453377, compound

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of the compound (8.35 g) obtained in Reference Example 1 in acetonitrile (100 mL), 1,8-diazabicyclo[5.4.0]undec-7-ene (4.58 mL) and lithium chloride (1.30 g) were added at room temperature. To this suspension, 1-trityl-1H-imidazole-4-carbaldehyde (6.90 g) was added, and the mixture was stirred overnight at room temperature. The solvent was distilled off under reduced pressure. To the residue, ethyl acetate and a 10% aqueous citric acid were added. This solution was separated into aqueous and organic layers. Then, the organic layer was washed with saturated sodium chloride solution, saturated aqueous sodium bicarbonate, and saturated sodium chloride solution in this order. The organic layer was dried over anhydrous sodium sulfate to obtain a mixture of tert-butyl (2E)-5-[(tert-butoxycarbonyl)amino]-2-[(1-trityl-1H-imidazol-4-yl)methylene]valerate and tert-butyl (2Z)-5-[(tert-butoxycarbonyl)amino]-2-[(1-trityl-1H-imidazol-4-yl)methylene]valerate (11.3 g). This mixture was suspended in methanol (500 mL). To this suspension, 10% palladium-carbon catalyst (hydrated, 4 g) was added, and the mixture was stirred at room temperature for 3 days under a hydrogen atmosphere. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluting solvent: methylene chloride/methanol=9/1) to obtain the title compound (5.60 g).

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. additionTo the residue, ethyl acetate and a 10% aqueous citric acid were added
  3. customThis solution was separated into aqueous and organic layers
  4. washThen, the organic layer was washed with saturated sodium chloride solution, saturated aqueous sodium bicarbonate, and saturated sodium chloride solution in this order
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customto obtain
  7. stirringthe mixture was stirred at room temperature for 3 days under a hydrogen atmosphere
  8. filtrationThe catalyst was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography (eluting solvent: methylene chloride/methanol=9/1)

Sources & evidence

ORD record
ord-7687887315154ac38b9d808a457fe9ab
Source dataset
uspto-grants-2013_12
Patent number
US08609710B2

Reaction notes

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