Sodium Chloride → Ethyl 1-((2'-cyano(1,1'-biphenyl)-4-yl)methyl)-4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate

HRID 1028478Notes

Reaction equation

HRID 1028478 reaction equation
[OH:1][C:2]([C:5]1[N:6]=[C:7]([CH2:15][CH2:16][CH3:17])[NH:8][C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH3:4])[CH3:3].[O-]CC.[Na+].Br[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[C:31]([C:36]#[N:37])=[CH:32][CH:33]=[CH:34][CH:35]=2)=[CH:26][CH:25]=1.[Cl-].[Na+]>C1(C)C=CC=CC=1.CN(C)C(=O)C>[C:36]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[C:27]1[CH:26]=[CH:25][C:24]([CH2:23][N:8]2[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:5]([C:2]([OH:1])([CH3:4])[CH3:3])[N:6]=[C:7]2[CH2:15][CH2:16][CH3:17])=[CH:29][CH:28]=1)#[N:37]

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 15019124'-(Bromomethyl)-2-cyanobiphenylHCID 2723922Sodium ethoxideHCID 178440079HCID 178440079, compound

Product 1

HCID 15461993Ethyl 1-((2'-cyano(1,1'-biphenyl)-4-yl)methyl)-4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylateYield 90.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 31374DimethylacetamideSolvent

Procedure

Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylate (8.09 g) obtained in Example 6 was dissolved in a mixture of toluene (28.3 ml) and N,N-dimethylacetamide (18 ml) under a nitrogen atmosphere, and to the reaction solution, sodium ethoxide (2.43 g) was added. After the reaction solution was stirred at room temperature for 1 hour, 4′-(bromomethyl)biphenyl-2-carbonitrile (9.70 g) was added, and the reaction solution was stirred at 40° C. for 4 hours. After the reaction solution was cooled to room temperature, it was poured into aqueous sodium chloride solution (5.4 wt %), and the aqueous layer was extracted with toluene. The organic layers were combined and concentrated under reduced pressure to approximately half the volume, subsequently Isopar E was added, then the mixture was stirred at room temperature for 16 hours, followed by further stirring for 1 hour under ice cooling. The precipitated crystals were collected by filtration, and subsequently dried under reduced pressure to afford the title compound (13.1 g) as white crystals.

Workup

  1. stirringthe reaction solution was stirred at 40° C. for 4 hours
  2. temperatureAfter the reaction solution was cooled to room temperature
  3. extractionthe aqueous layer was extracted with toluene
  4. concentrationconcentrated under reduced pressure to approximately half the volume, subsequently Isopar E
  5. additionwas added
  6. stirringthe mixture was stirred at room temperature for 16 hours
  7. stirringby further stirring for 1 hour under ice cooling
  8. filtrationThe precipitated crystals were collected by filtration
  9. customsubsequently dried under reduced pressure

Sources & evidence

ORD record
ord-65c88cc2dd774ccaafd34c97c281411a
Source dataset
uspto-grants-2014_05
Patent number
US08735598B2

Reaction notes

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