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

HRID 243781Notes

Reaction equation

HRID 243781 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.ClC1C(Cl)=C([Li])C(C(F)(F)F)=CN=1.[CH3:38][O:39][C:40]1[C:47]([O:48][CH3:49])=[C:46]([O:50][CH3:51])[CH:45]=[C:44]([CH3:52])[C:41]=1[CH:42]=[O:43]>O.C1(C)C=CC=CC=1.C(OCC)C>[CH3:38][O:39][C:40]1[C:47]([O:48][CH3:49])=[C:46]([O:50][CH3:51])[CH:45]=[C:44]([CH3:52])[C:41]=1[CH:42]([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:43]

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 896832,3,4-Trimethoxy-6-methylbenzaldehydeHCID 1122342,3-Dichloro-5-(trifluoromethyl)pyridineHCID 178418339ButyllithiumHCID 178506748HCID 178506748, compound

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 mol/l hexane solution) was dropwise added at 0° C. to a diethyl ether 120 ml solution of 15.0 ml (107 mmol) of diisopropylamine, followed by stirring for 1 hour. The solution was cooled to −78° C., and a diethyl ether 10 ml solution of 22.1 g (102 mmol) of 2,3-dichloro-5-trifluoromethylpyridine was added, followed by stirring for 30 minutes to prepare 2,3-dichloro-5-trifluoromethyl-4-pyridyllithium, and then a toluene 40 ml solution of 21.0 g (100 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde was added, followed by stirring for 2 hours. 30 ml of water was added to the mixture to terminate the reaction, and the aqueous layer was extracted with ethyl acetate. 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 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 (melting point 95 to 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 materialThen, the 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 was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5ec8d2aad65e4d25995401d19c5312d7
Source dataset
uspto-grants-2014_02
Patent number
US08653277B2

Reaction notes

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