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

HRID 243775Notes

Reaction equation

HRID 243775 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Br:13][C:14]1[C:15]([C:22]([F:25])([F:24])[F:23])=[CH:16][C:17]([O:20][CH3:21])=[N:18][CH:19]=1.FC(F)(F)C1C=CN=C(OC)C=1.BrC1C(C(F)(F)F)=C([Li])C(OC)=NC=1.FC(F)(F)C1C=CN=C(OC)C=1[Li].[CH3:65][O:66][C:67]1[C:74]([O:75][CH3:76])=[C:73]([O:77][CH3:78])[CH:72]=[C:71]([CH3:79])[C:68]=1[CH:69]=[O:70]>O1CCCC1.O>[CH3:65][O:66][C:67]1[C:74]([O:75][CH3:76])=[C:73]([O:77][CH3:78])[CH:72]=[C:71]([CH3:79])[C:68]=1[CH:69]([C:16]1[C:17]([O:20][CH3:21])=[N:18][CH:19]=[C:14]([Br:13])[C:15]=1[C:22]([F:25])([F:23])[F:24])[OH:70]

Participants

10

Reactant 7

HCID 7912DiisopropylamineHCID 896832,3,4-Trimethoxy-6-methylbenzaldehydeHCID 18539797Pyridine, 2-methoxy-4-(trifluoromethyl)-HCID 230826445-Bromo-2-methoxy-4-(trifluoromethyl)pyridineHCID 178418339ButyllithiumHCID 178506747HCID 178506747, compoundHCID 178506768HCID 178506768, compound

Product 1

HCID 23082661(2,3,4-Trimethoxy-6-methylphenyl)(5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyl)methanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

17.1 ml of n-butyllithium (1.57 mol/l hexane solution) was dropwise added at 0° C. to a solution having 3.80 ml (27.1 mmol) of diisopropylamine dissolved in 50 ml of tetrahydrofuran, followed by stirring for 30 minutes. The solution was cooled to −78° C., and a solution having 5.81 g of the mixture of 5-bromo-4-trifluoromethyl-2-methoxypyridine and 4-trifluoromethyl-2-methoxypyridine (molar ratio 55:45) obtained in Step (c) dissolved in 10 ml of tetrahydrofuran was added, followed by stirring for 45 minutes to prepare a mixture of 5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyllithium and 4-trifluoromethyl-2-methoxy-3-pyridyllithium. A solution having 5.51 g (26.2 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 15 ml of tetrahydrofuran was added, followed by stirring for 1 hour. Water was added to the mixture to terminate the reaction, and tetrahydrofuran was distilled off under reduced pressure. After extraction with ethyl acetate, 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 5.02 g of (2,3,4-trimethoxy-6-methylphenyl)(5-bromo-4-trifluoromethyl-2-methoxy-3-pyridyl)methanol.

Workup

  1. customobtained in Step (c)
  2. additionwas added
  3. stirringby stirring for 45 minutes
  4. customto prepare
  5. additionwas added
  6. stirringby stirring for 1 hour
  7. customto terminate
  8. customthe reaction, and tetrahydrofuran
  9. distillationwas distilled off under reduced pressure
  10. extractionAfter extraction with ethyl acetate
  11. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  12. filtrationsubjected to filtration
  13. distillationthe solvent was distilled off under reduced pressure
  14. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3f2b8029c52b44b48ced90a72b0e767a
Source dataset
uspto-grants-2014_02
Patent number
US08653277B2

Reaction notes

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