Indomethacin → [1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetoxy]-benzyl acetate

HRID 1659168Notes

Reaction equation

HRID 1659168 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:19][C:20]([OH:22])=[O:21])=[C:9]2[CH3:23])=[O:7])=[CH:4][CH:3]=1.Br[CH2:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29]>CN(C)C=O>[C:28]([O:30][CH:31]([O:21][C:20](=[O:22])[CH2:19][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)[N:8]([C:6](=[O:7])[C:5]2[CH:24]=[CH:25][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:9]=1[CH3:23])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)(=[O:29])[CH3:27]

Participants

4

Reactant 2

HCID 3715IndomethacinHCID 62576Benzyl bromoacetate

Product 1

HCID 70621351[1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetoxy]-benzyl acetateYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

180 g (0.503 mol) of 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetic acid were dissolved in 900 ml of dimethylformamide, 35 g of triturated, anhydrous potassium carbonate were added and stirring was continued for 45 minutes at 50°C. 128 g (0.558 mol) of benzyl bromoacetate were then added and the mixture was stirred for 3 hours at 50°C. After evaporating the dimethylformamide under vacuum, the residue was dissolved in chloroform, washed several times with water, dried over sodium sulphate and then separated by chromatography on alumina. The eluate was concentrated by evaporation and the residue recrystallised from alcohol. The [1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetoxy]-benzyl acetate which formed melted at 93°-94°C and the yield was 81% of the theoretical. This benzyl ester was converted as described in Example 1 or 2 into the free acid.

Workup

  1. custom35 g of triturated
  2. additionanhydrous potassium carbonate were added
  3. stirringthe mixture was stirred for 3 hours at 50°C
  4. customAfter evaporating the dimethylformamide under vacuum
  5. dissolutionthe residue was dissolved in chloroform
  6. washwashed several times with water
  7. dry with materialdried over sodium sulphate
  8. customseparated by chromatography on alumina
  9. concentrationThe eluate was concentrated by evaporation
  10. customthe residue recrystallised from alcohol

Sources & evidence

ORD record
ord-038516c5af724dfc99e212bf9d662c9f
Source dataset
uspto-grants-1976_06
Patent number
US03966956

Reaction notes

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