Diisopropylamine → (2,3,4-Trimethoxy-6-methylphenyl)(2,6-dichloro-4-trifluoromethyl-3-pyridyl)methanol

HRID 1835396Notes

Reaction equation

HRID 1835396 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[C:16]([Cl:24])[N:15]=1.[CH3:25][O:26][C:27]1[C:34]([O:35][CH3:36])=[C:33]([O:37][CH3:38])[CH:32]=[C:31]([CH3:39])[C:28]=1[CH:29]=[O:30]>O1CCCC1.O>[CH3:25][O:26][C:27]1[C:34]([O:35][CH3:36])=[C:33]([O:37][CH3:38])[CH:32]=[C:31]([CH3:39])[C:28]=1[CH:29]([C:19]1[C:14]([Cl:13])=[N:15][C:16]([Cl:24])=[CH:17][C:18]=1[C:20]([F:21])([F:22])[F:23])[OH:30]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 896832,3,4-Trimethoxy-6-methylbenzaldehydeHCID 5209682,6-Dichloro-4-(trifluoromethyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 12151532(2,3,4-Trimethoxy-6-methylphenyl)(2,6-dichloro-4-trifluoromethyl-3-pyridyl)methanolYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

14 ml (20 mmol) of n-butyllithium (1.5 M hexane solution) was dropwise added at 0° C. to a solution having 2.9 ml (21 mmol) of diisopropylamine dissolved in 62 ml of tetrahydrofuran, followed by stirring for 30 minutes. The solution was cooled to −20° C., a solution having 4.0 g (19 mmol) of 2,6-dichloro-4-trifluoromethylpyridine dissolved in 5 ml of tetrahydrofuran was added thereto, followed by stirring for 5 minutes, and a solution having 3.8 g (18 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 7 ml of tetrahydrofuran was added thereto, followed by stirring for 1.5 hours. 30 ml of water was added to the mixture to terminate the reaction, and tetrahydrofuran was distilled off under reduced pressure. Extraction with ethyl acetate was carried out, the organic layer was dried over anhydrous sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography to obtain 6.2 g (yield 81%) of (2,3,4-trimethoxy-6-methylphenyl)(2,6-dichloro-4-trifluoromethyl-3-pyridyl)methanol (brown oily substance).

Workup

  1. additionwas added
  2. stirringby stirring for 5 minutes
  3. additionwas added
  4. stirringby stirring for 1.5 hours
  5. customto terminate
  6. customthe reaction, and tetrahydrofuran
  7. distillationwas distilled off under reduced pressure
  8. extractionExtraction with ethyl acetate
  9. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  10. filtrationsubjected to filtration
  11. distillationthe solvent was distilled off under reduced pressure
  12. customThe crude product thus obtained
  13. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ebb93dec41ef4589aa5f455473bf4b76
Source dataset
uspto-grants-2004_08
Patent number
US06770662B2

Reaction notes

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