Potassium Carbonate → 1-(2,2-Dimethyl-4-chloro-indan-1-yl)-5-imidazolecarboxylic acid methyl ester

HRID 5778Notes

Reaction equation

HRID 5778 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]([NH:9][CH:10]=[N:11][CH:12]1[C:20]2[C:15](=[C:16]([Cl:21])[CH:17]=[CH:18][CH:19]=2)[CH2:14][C:13]1([CH3:23])[CH3:22])#N.Br[CH2:25][C:26]([O:28][CH3:29])=[O:27]>CN(C)C=O>[CH3:29][O:28][C:26]([C:25]1[N:11]([CH:12]2[C:20]3[C:15](=[C:16]([Cl:21])[CH:17]=[CH:18][CH:19]=3)[CH2:14][C:13]2([CH3:23])[CH3:22])[CH:10]=[N:9][CH:7]=1)=[O:27]

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 60984Methyl bromoacetateHCID 19794092N-cyano-N'-(2,2-dimethyl-4-chloroindan-1-yl)formamidine

Product 1

HCID 537167311-(2,2-Dimethyl-4-chloro-indan-1-yl)-5-imidazolecarboxylic acid methyl esterYield 49.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

12.7 g of potassium carbonate are added to a solution of 21 g of N-cyano-N'-(2,2-dimethyl-4-chloroindan-1-yl)formamidine in 80 ml of dimethylformamide. 14.1 g of methyl bromoacetate are added dropwise. After the exothermic reaction has ceased the mixture is agitated for 1.5 hours at +50° C. another portion of 12.7 g of potassium carbonate is added and the mixture is stirred for 18 hours at +100° C. The precipitate is filtered off from the hot solution and washed with 30 g of hot dimethylformamide. The combined filtrates are dropwise added at +60° C. to a solution of 14.2 g of tert. butylnitrite in 30 ml of dimethylformamide. Immediate evolution of nitrogen is observed and the temperature of the mixture rises to +67° C. After 30 minutes the dropwise addition is completed. The mixture is maintained at +70° to +75° C. for 2.5 hours and then poured into ice-water and extracted with ethyl acetate. The organic phase is washed with brine, dried with sodium sulfate and concentrated to dryness. The residue is purified by chromatography at a silica gel column with an ethyl acetate/hexane mixture (1:2 by volume), affording 12.7 g of 1-(2,2-dimethyl-4-chloro-indan-1-yl)-5-imidazolecarboxylic acid methyl ester, having a melting point of 111°-113° C.

Workup

  1. customAfter the exothermic reaction
  2. additionis added
  3. filtrationThe precipitate is filtered off from the hot solution
  4. washwashed with 30 g of hot dimethylformamide
  5. additionThe combined filtrates are dropwise added at +60° C. to a solution of 14.2 g of tert. butylnitrite in 30 ml of dimethylformamide
  6. customrises to +67° C
  7. additionAfter 30 minutes the dropwise addition
  8. temperatureThe mixture is maintained at +70° to +75° C. for 2.5 hours
  9. additionpoured into ice-water
  10. extractionextracted with ethyl acetate
  11. washThe organic phase is washed with brine
  12. dry with materialdried with sodium sulfate
  13. concentrationconcentrated to dryness
  14. customThe residue is purified by chromatography at a silica gel column with an ethyl acetate/hexane mixture (1:2 by volume)

Sources & evidence

ORD record
ord-085932d48bf14331abdf9a25304a46c5
Source dataset
uspto-grants-1993_09
Patent number
US05246915

Reaction notes

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