5-Methylimidazo(1,5-a)pyridine → 5-(5-Ethoxycarbonylpentyl)imidazo[1,5-a]pyridine

HRID 326116Notes

Reaction equation

HRID 326116 reaction equation
[CH3:1][C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[Li]CC1N2C=NC=C2C=CC=1.Br[CH2:28][CH2:29][CH2:30][CH2:31][C:32](OCC)([O:36]CC)[O:33][CH2:34][CH3:35]>O1CCCC1.CCCCCC>[CH2:34]([O:33][C:32]([CH2:31][CH2:30][CH2:29][CH2:28][CH2:1][C:2]1[N:7]2[CH:8]=[N:9][CH:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1)=[O:36])[CH3:35]

Participants

7

Reactant 4

HCID 122109855-Methylimidazo(1,5-a)pyridineHCID 132061375-Bromo-1,1,1-triethoxypentaneHCID 178418339ButyllithiumHCID 178506849HCID 178506849, compound

Product 1

HCID 132061385-(5-Ethoxycarbonylpentyl)imidazo[1,5-a]pyridine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of 50 g of 5-methylimidazo[1,5-a]pyridine [J. Org. Chem. 40, 1210 (1975)] in 625 ml of tetrahydrofuran precooled to -75° is added under nitrogen atmosphere 175 ml of 2.4 N n-butyllithium in hexane while maintaining temperature below -53°. The solution of 5-(lithiomethyl)imidazo[1,5-a]pyridine, is cooled back to -75° and a solution of 121.8 g of 5-bromo-1,1,1-triethoxypentane in 125 ml of tetrahydrofuran is added rapidly at which time the temperature rises to -60°. The reaction mixture is allowed to warm to -4° over a 45 minute period and evaporated practically to dryness. The residue is partitioned between 500 ml of ethyl ether and 240 ml of 3 N hydrochloric acid. The ether solution is further extracted twice with 60 ml of 3 N hydrochloric acid; the combined aqueous extract is basified with 100 ml of concentrated ammonia hydroxide and reextracted twice with 200 ml of ethyl ether. The ether extract is dried over magnesium sulfate and evaporated to dryness to give an oil which is distilled under high vacuum to give 5-(5-ethoxycarbonylpentyl)-imidazo[1,5-a]pyridine boiling at 180°-5°/0.12 mm Hg.

Workup

  1. customprecooled to -75°
  2. temperaturewhile maintaining temperature below -53°
  3. customrises to -60°
  4. temperatureto warm to -4° over a 45 minute period
  5. customevaporated practically to dryness
  6. customThe residue is partitioned between 500 ml of ethyl ether and 240 ml of 3 N hydrochloric acid
  7. extractionThe ether solution is further extracted twice with 60 ml of 3 N hydrochloric acid
  8. extractionthe combined aqueous extract
  9. extractionThe ether extract
  10. dry with materialis dried over magnesium sulfate
  11. customevaporated to dryness
  12. customto give an oil which
  13. distillationis distilled under high vacuum

Sources & evidence

ORD record
ord-26741a9f521c42c6a7098b19d54b8423
Source dataset
uspto-grants-1984_04
Patent number
US04444775

Reaction notes

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