1-Bromo-3-chloropropane → 5-(3-Chloro-propoxy)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic Acid Ethyl Ester

HRID 1437685Notes

Reaction equation

HRID 1437685 reaction equation
[CH3:1][CH2:2][O:3][C:4]([C:6]1[N:15](C(OC(C)(C)C)=O)[C:9]2=[N:10][CH:11]=[C:12]([OH:14])[CH:13]=[C:8]2[CH:7]=1)=[O:5].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][CH2:31][CH2:32][Cl:33].[Cl-].[NH4+]>CC(=O)CC>[CH2:2]([O:3][C:4]([C:6]1[NH:15][C:9]2=[N:10][CH:11]=[C:12]([O:14][CH2:30][CH2:31][CH2:32][Cl:33])[CH:13]=[C:8]2[CH:7]=1)=[O:5])[CH3:1]

Participants

6

Reactant 4

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 684243571H-Pyrrolo[2,3-b]pyridine-1,2-dicarboxylic acid, 5-hydroxy-, 1-(1,1-dimethylethyl) 2-ethyl ester

Product 1

HCID 684233145-(3-Chloro-propoxy)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic Acid Ethyl EsterYield 32.4%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

The suspension consistent of 0.5 g (2.4 mmol) 5-hydroxy-pyrrolo[2,3-b]pyridine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (as prepared in WO 05/000849), 0.4 g (2.6 mmol) potassium carbonate and 0.29 ml (0.46 g, 2.9 mmol) 1-bromo-3-chloropropane in 10 ml 2-butanone was heated under reflux for 23 hours. The reaction mixture was poured on 10% aqueous ammonium chloride solution and was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was flash-chromatographed on silica gel with n-heptane:ethyl acetate (1:1 v/v) as eluant to give 0.22 g (32%) of the desired compound as a colorless solid.

Workup

  1. temperatureunder reflux for 23 hours
  2. extractionwas extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was flash-chromatographed on silica gel with n-heptane:ethyl acetate (1:1 v/v) as eluant

Sources & evidence

ORD record
ord-46a7a713c3f94c5a9ece1db084dd7095
Source dataset
uspto-grants-2009_11
Patent number
US07622466B2

Reaction notes

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