2,4,6-Trimethylpyridine → HCID 22398636, compound

HRID 1510894Notes

Reaction equation

HRID 1510894 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.C([Li])(C)(C)C.[F:15][C:16]1[CH:17]=[CH:18][C:19]([O:29][CH3:30])=[C:20]([C:22]([CH3:28])([CH3:27])[CH2:23][C:24](=[O:26])[CH3:25])[CH:21]=1>C1COCC1>[F:15][C:16]1[CH:17]=[CH:18][C:19]([O:29][CH3:30])=[C:20]([C:22]([CH3:27])([CH3:28])[CH2:23][C:24]([CH2:1][C:2]2[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=2)([OH:26])[CH3:25])[CH:21]=1

Participants

5

Reactant 3

HCID 79532,4,6-TrimethylpyridineHCID 222849224-(5-Fluoro-2-methoxyphenyl)-4-methylpentan-2-oneHCID 178418306HCID 178418306, compound

Product 1

HCID 22398636HCID 22398636, compoundYield 56.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

To a solution of 2,4,6-trimethylpyridine (0.14 g) in THF (1 mL) stirred under argon and cooled to −70° C., tert-butyl lithium (1.7M in pentane, 0.75 mL) was added dropwise over 2 minutes. After stirring for an additional 2 minutes, 4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (Example 17) (0.22 g) in THF (0.8 mL) was added all at once. After 5 minutes, the reaction was quenched with EtOH (0.2 mL) and allowed to warm to room temperature. The mixture was diluted with EtOAc, washed with water, dried, filtered, and evaporated. Chromatography of the residue over silica gel (eluent: EtOAc-methylene chloride (2:98 to 8:92 gradient)) gave the product as an oil (0.19 g).

Workup

  1. waitAfter 5 minutes
  2. customthe reaction was quenched with EtOH (0.2 mL)
  3. temperatureto warm to room temperature
  4. additionThe mixture was diluted with EtOAc
  5. washwashed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-4c9ac70d3ab34236803cee7f0112182d
Source dataset
uspto-grants-2012_07
Patent number
US08212040B2

Reaction notes

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