1,1'-Carbonyldiimidazole → HCID 67316730, compound

HRID 533283Notes

Reaction equation

HRID 533283 reaction equation
[C:1]1([O:11][CH2:12][CH2:13][CH2:14][N:15]2[C:23]3[C:18](=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH3:30])[CH:20]=[CH:21][CH:22]=3)[CH:17]=[C:16]2C(O)=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[C:46]([O:52][CH2:53][CH3:54])(=[O:51])[CH2:47][C:48]([O-])=[O:49].[K+].[Cl-].[Mg+2].[Cl-]>O1CCCC1.C(#N)C.C(N(CC)CC)C>[C:1]1([O:11][CH2:12][CH2:13][CH2:14][N:15]2[C:23]3[C:18](=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH3:30])[CH:20]=[CH:21][CH:22]=3)[CH:17]=[C:16]2[C:48](=[O:49])[CH2:47][C:46]([O:52][CH2:53][CH3:54])=[O:51])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium ChlorideHCID 25099972HCID 25099972, compound

Product 1

HCID 67316730HCID 67316730, compound

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 1-(3-(naphthalen-1-yloxy)propyl)-4-o-tolyl-1H-indole-2-carboxylic acid (EXAMPLE 103) (536 mg) and 1,1′-carbonyldiimidazole (200 mg) in tetrahydrofuran (10 ml) was stirred at room temperature. overnight. To a suspension of potassium ethyl malonate (419 mg) in acetonitrile (10 ml) and triethylamine (0.515 ml) was added magnesium chloride (300 mg) and the mixture was stirred at room temperature for 4 hours then cooled in an ice bath. The above-prepared solution was added dropwise to the first solution, and the resultant suspension was stirred at room temperature for three days. After this time the solvent was removed in vacuo, the residue was taken up in toluene (50 ml), cooled (ice bath), and aqueousHCl (12%) was slowly added. The mixture was warmed to room temperature and extracted twice with ethyl acetate. The combined layers were washed with aqueous NaHCO3, and brine and dried over Na2SO4. After concentration of the solvent, the residue was loaded on a column and eluted with 5% ethyl acetate in hexane to give the title compound.

Workup

  1. customovernight
  2. temperaturethen cooled in an ice bath
  3. additionThe above-prepared solution was added dropwise to the first solution
  4. customAfter this time the solvent was removed in vacuo
  5. temperaturecooled (ice bath), and aqueousHCl (12%)
  6. additionwas slowly added
  7. temperatureThe mixture was warmed to room temperature
  8. extractionextracted twice with ethyl acetate
  9. washThe combined layers were washed with aqueous NaHCO3, and brine
  10. dry with materialdried over Na2SO4
  11. washeluted with 5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-a2cc4ea2031f41b882c4e414e8f3f04b
Source dataset
uspto-grants-2014_10
Patent number
US08853209B2

Reaction notes

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