Diisopropylamine → 4,5-Dichloro-2-methoxy-alpha-(2,3,4-trimethoxy-6-methylphenyl)-3-pyridinemethanol

HRID 1912251Notes

Reaction equation

HRID 1912251 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([O:21][CH3:22])[CH:15]=1.ClC1C(Cl)=CN=C(OC)C=1[Li].[CH3:34][O:35][C:36]1[C:43]([O:44][CH3:45])=[C:42]([O:46][CH3:47])[CH:41]=[C:40]([CH3:48])[C:37]=1[CH:38]=[O:39]>O1CCCC1.O>[CH3:34][O:35][C:36]1[C:43]([O:44][CH3:45])=[C:42]([O:46][CH3:47])[CH:41]=[C:40]([CH3:48])[C:37]=1[CH:38]([C:15]1[C:16]([O:21][CH3:22])=[N:17][CH:18]=[C:19]([Cl:20])[C:14]=1[Cl:13])[OH:39]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 896832,3,4-Trimethoxy-6-methylbenzaldehydeHCID 230825824,5-Dichloro-2-methoxypyridineHCID 178418339ButyllithiumHCID 178506770HCID 178506770, compound

Product 1

HCID 230826084,5-Dichloro-2-methoxy-alpha-(2,3,4-trimethoxy-6-methylphenyl)-3-pyridinemethanolYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

15.1 ml of n-butyllithium (1.57 mol/l hexane solution) was dropwise added at −20° C. to a solution having 2.40 g (23.7 mmol) of diisopropylamine dissolved in 30 ml of tetrahydrofuran, followed by stirring for 1 hour. The solution was cooled to −78° C., and a solution having 4.22 g (23.6 mmol) of 4,5-dichloro-2-methoxypyridine obtained in Step (e) dissolved in 20 ml of tetrahydrofuran was added, followed by stirring for 2 hours to prepare 4,5-dichloro-2-methoxy-3-pyridyllithium. Then, to this solution, a solution having 5.00 g (23.8 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 20 ml of tetrahydrofuran was added, followed by stirring for 30 minutes. 50 ml of water was added to the mixture to terminate the reaction, and tetrahydrofuran was distilled off under reduced pressure. After extraction with ethyl ether, the organic layer was dried over sodium sulfate and subjected to filtration, and the solvent was distilled off under reduced pressure, followed by purification by silica gel column chromatography to obtain 4.66 g (yield: 51%) of (2,3,4-trimethoxy-6-methylphenyl)(4,5-dichloro-2-methoxy-3-pyridyl)methanol.

Workup

  1. additionwas added
  2. stirringby stirring for 2 hours
  3. additionwas added
  4. stirringby stirring for 30 minutes
  5. customto terminate
  6. customthe reaction, and tetrahydrofuran
  7. distillationwas distilled off under reduced pressure
  8. extractionAfter extraction with ethyl ether
  9. dry with materialthe organic layer was dried over sodium sulfate
  10. filtrationsubjected to filtration
  11. distillationthe solvent was distilled off under reduced pressure
  12. customfollowed by purification by silica gel column chromatography

Sources & evidence

ORD record
ord-94dd9fa5a33c46b5ab8786791f466c23
Source dataset
uspto-grants-2013_12
Patent number
US08609150B2

Reaction notes

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