Propanal → HCID 58478773, compound

HRID 1011406Notes

Reaction equation

HRID 1011406 reaction equation
CC1(C)CCCC(C)(C)N1.[Li][CH2:12][CH2:13][CH2:14][CH3:15].[N:16]1[CH:21]=[CH:20][CH:19]=C[C:17]=1[C:22]([OH:24])=[O:23].C(=O)CC>C1COCC1>[CH2:14]([CH:13]1[C:12]2[C:17](=[N:16][CH:21]=[CH:20][CH:19]=2)[C:22](=[O:23])[O:24]1)[CH3:15]

Participants

6

Reactant 4

HCID 527PropanalHCID 1018Picolinic acidHCID 130352,2,6,6-TetramethylpiperidineHCID 178418339Butyllithium

Product 1

HCID 58478773HCID 58478773, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 2,2,6,6-tetramethyl-piperidine (20.3 ml, 120 mmol) in a 250 ml round bottomed flask equipped with a magnetic stirrer, is put under argon atmosphere and 60 ml of dry THF is added. The reaction mixture is cooled to −78° C. The cooled reaction mixture is treated dropwise with nBuLi solution (64 mL of a 2.5 M solution in hexanes, 160 mmol) and the reaction is let stir at −78° C. for 5 min. A solution of picolinic acid (4.92 g, 40 mmol) in THF (60 mL) is added dropwise to the reaction at −78° C. The reaction is stirred at −78° C. for 1 h and is then warmed to −20° C. for 30 min. The reaction mixture is treated with propionaldehyde (7.2 ml, 100 mmol, 2.5 eq) dropwise at −50° C. The reaction is stirred at −20° C. for 2 h and warmed to room temperature overnight. The reaction mixture is concentrated and the residue is dissolved in water and ether. The aqueous layer is collected and extracted with dichloromethane and ether (6×50 ml). The aqueous phase is concentrated and the residue is dissolved in EtOH (30 mL) and acetic acid (2 mL) and heated at reflux overnight under argon. The reaction mixture is cooled to room temperature and concentrated. The residue is purified by chromatography (silica gel) to give the title compound (0.70 g, 11%).

Workup

  1. customThe cooled reaction mixture
  2. stirringThe reaction is stirred at −78° C. for 1 h
  3. temperatureis then warmed to −20° C. for 30 min
  4. stirringThe reaction is stirred at −20° C. for 2 h
  5. temperaturewarmed to room temperature overnight
  6. concentrationThe reaction mixture is concentrated
  7. dissolutionthe residue is dissolved in water
  8. customThe aqueous layer is collected
  9. extractionextracted with dichloromethane and ether (6×50 ml)
  10. concentrationThe aqueous phase is concentrated
  11. dissolutionthe residue is dissolved in EtOH (30 mL)
  12. temperatureacetic acid (2 mL) and heated
  13. temperatureat reflux overnight under argon
  14. temperatureThe reaction mixture is cooled to room temperature
  15. concentrationconcentrated
  16. customThe residue is purified by chromatography (silica gel)

Sources & evidence

ORD record
ord-3bbb20c1fee1428080894cd9bab86b79
Source dataset
uspto-grants-2011_07
Patent number
US07977351B2

Reaction notes

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