Ammonium Chloride → 2-(2-Chloropyridin-5-yl)-1-(3-methoxy-5-methylphenyl)ethanone

HRID 2390784Notes

Reaction equation

HRID 2390784 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH3:13])[CH:12]=1)[C:6]([O:8]C)=O.[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][N:16]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[Cl-].[NH4+]>O1CCCC1>[Cl:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:6]([C:5]2[CH:10]=[C:11]([CH3:13])[CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)=[O:8])=[CH:17][N:16]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 5813932-Chloro-5-methyl-pyridineHCID 2733832Lithium HexamethyldisilazideHCID 13834966Methyl 3-methoxy-5-methylbenzoate

Product 1

HCID 508989412-(2-Chloropyridin-5-yl)-1-(3-methoxy-5-methylphenyl)ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 3-methoxy-5-methylbenzoate (9.0 g, 50 mmol) and 2-chloro-5-methylpyridine (7.0 g, 55 mmol) in tetrahydrofuran (90 mL) was dropwise added lithium hexamethyldisilazide (75 mL, 75 mmol, 1M In THF) at 0° C. under nitrogen atmosphere, and stirred at room temperature for 18 hours. After completion of the nucleophilic attack reaction, the reaction mixture was neutralized with a saturated ammonium chloride solution (150 mL) and extracted with ethyl acetate (300 mL×2). The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated by vacuum distillation, and the concentrate (7.58 g, 55%) was used in the next reaction without further purification.

Workup

  1. customat 0° C.
  2. customAfter completion of the nucleophilic attack reaction
  3. extractionextracted with ethyl acetate (300 mL×2)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated by vacuum distillation
  7. concentrationthe concentrate (7.58 g, 55%)
  8. customwas used in the next reaction without further purification

Sources & evidence

ORD record
ord-085ce3da51234f4398315acdd025283a
Source dataset
uspto-grants-2012_09
Patent number
US08273880B2

Reaction notes

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