Diisopropylamine → (2,3,4-Trimethoxy-6-methylphenyl)(2,3-dichloro-5-trifluoromethyl-4-pyridyl)methanol

HRID 1835415Notes

Reaction equation

HRID 1835415 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[CH:16][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]>O.C1(C)C=CC=CC=1.C(OCC)C>[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:18]1[C:17]([C:21]([F:24])([F:22])[F:23])=[CH:16][N:15]=[C:14]([Cl:13])[C:19]=1[Cl:20])[OH:30]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 896832,3,4-Trimethoxy-6-methylbenzaldehydeHCID 1122342,3-Dichloro-5-(trifluoromethyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 12151301(2,3,4-Trimethoxy-6-methylphenyl)(2,3-dichloro-5-trifluoromethyl-4-pyridyl)methanolYield 58.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

70.0 ml (106 mmol) of n-butyllithium (1.5 M hexane solution) was dropwise added to a diethyl ether 120 ml solution of 15.0 ml (107 mmol) of diisopropylamine at 0° C., followed by stirring for 1 hour. The solution was cooled to −78° C., a diethyl ether 10 ml solution of 22.1 g (102 mmol) of 2,3-dichloro-5-trifluoromethylpyridine was added thereto, followed by stirring for 30 minutes, and then a toluene 40 ml solution of 21.0 g (100 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde was added thereto, followed by stirring for 2 hours. 30 ml of water was added to the mixture to terminate the reaction, the aqueous layer was extracted with ethyl acetate, and then 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 24.8 g (yield 58%) of (2,3,4-trimethoxy-6-methylphenyl)(2,3-dichloro-5-trifluoromethyl-4-pyridyl)methanol (m.p. 95-98° C.).

Workup

  1. stirringby stirring for 30 minutes
  2. stirringby stirring for 2 hours
  3. customto terminate
  4. customthe reaction
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  7. filtrationsubjected to filtration
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe crude product thus obtained
  10. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b9f64072f4524f6a8f8d276d3888678e
Source dataset
uspto-grants-2004_08
Patent number
US06770662B2

Reaction notes

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