Triethylamine → (2,3,4-Trimethoxy-6-methylphenyl)(5-chloro-2-methoxy-4-methyl-3-pyridyl)methanol

HRID 242422Notes

Reaction equation

HRID 242422 reaction equation
C(N(CC)CC)C.C([Mg]Cl)(C)C.Br[C:14]1[C:15]([O:22][CH3:23])=[N:16][CH:17]=[C:18]([Cl:21])[C:19]=1[CH3:20].ClC1C(C)=C([Mg]Cl)C(OC)=NC=1.[CH3:36][O:37][C:38]1[C:45]([O:46][CH3:47])=[C:44]([O:48][CH3:49])[CH:43]=[C:42]([CH3:50])[C:39]=1[CH:40]=[O:41]>O1CCCC1.O>[CH3:36][O:37][C:38]1[C:45]([O:46][CH3:47])=[C:44]([O:48][CH3:49])[CH:43]=[C:42]([CH3:50])[C:39]=1[CH:40]([C:14]1[C:15]([O:22][CH3:23])=[N:16][CH:17]=[C:18]([Cl:21])[C:19]=1[CH3:20])[OH:41]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 896832,3,4-Trimethoxy-6-methylbenzaldehydeHCID 231336453-Bromo-5-chloro-2-methoxy-4-methylpyridineHCID 178418918HCID 178418918, compoundHCID 178494194HCID 178494194, compound

Product 1

HCID 23082593(2,3,4-Trimethoxy-6-methylphenyl)(5-chloro-2-methoxy-4-methyl-3-pyridyl)methanolYield 71.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

4 ml of tetrahydrofuran and 0.62 ml (4.4 mmol) of triethylamine were added to 2.2 ml (4.4 mmol) of isopropylmagnesium chloride (2.0 mol/l tetrahydrofuran solution), the mixture was cooled to 0° C., and a solution having 1.0 g (4.2 mmol) of 3-bromo-5-chloro-2-methoxy-4-methylpyridine dissolved in 5 ml of tetrahydrofuran was dropwise added, followed by stirring for 3 hours to prepare 5-chloro-2-methoxy-4-methyl-3-pyridylmagnesium chloride. A solution having 0.89 g (4.2 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 5 ml of tetrahydrofuran was dropwise added to the reaction solution, followed by stirring for 1 hour, and then the temperature was increased to room temperature, followed by stirring further for 1 hour. Water was added to the reaction solution to terminate the reaction, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous magnesium 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 1.1 g (yield: 70%) of (2,3,4-trimethoxy-6-methylphenyl)(5-chloro-2-methoxy-4-methyl-3-pyridyl)methanol (pale yellow oily substance).

Workup

  1. additionwas dropwise added
  2. additionwas dropwise added to the reaction solution
  3. stirringby stirring for 1 hour
  4. temperaturethe temperature was increased to room temperature
  5. stirringby stirring further for 1 hour
  6. customto terminate
  7. customthe reaction
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe organic layer was washed with a saturated sodium chloride solution
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationsubjected to filtration
  12. distillationthe solvent was distilled off under reduced pressure
  13. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-3988162d8eac44578fa99d1dd9f29a66
Source dataset
uspto-grants-2014_02
Patent number
US08653113B2

Reaction notes

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