4-Methylpyridine → 1-(3-Dibenzylamino-2,6-difluoro-phenyl)-2-pyridin-4-yl-ethanone

HRID 45843

Reaction equation

HRID 45843 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].C([O:25][C:26](=O)[C:27]1[C:32]([F:33])=[CH:31][CH:30]=[C:29]([N:34]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:28]=1[F:49])C1C=CC=CC=1.[Cl-].[NH4+]>O1CCCC1>[CH2:42]([N:34]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:29]1[C:28]([F:49])=[C:27]([C:26](=[O:25])[CH2:1][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=2)[C:32]([F:33])=[CH:31][CH:30]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

6

Reactant 4

HCID 79634-Methylpyridine2×HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 584771183-Dibenzylamino-2,6-difluoro-benzoic acid benzyl ester

Product 1

HCID 584771201-(3-Dibenzylamino-2,6-difluoro-phenyl)-2-pyridin-4-yl-ethanoneYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To 4-methyl-pyridine (806 4, 8.33 mmol) in anhydrous tetrahydrofuran (35 mL) was added at 0° C. sodium hexamethyldisilazide 1 M in tetrahydrofuran (16.66 mL, 16.66 mmol) and the reaction was stirred for 20 minutes. 3-Dibenzylamino-2,6-difluoro-benzoic acid benzyl ester (3.691 g, 8.33 mmol) was dissolved in tetrahydrofuran (5 mL) and added dropwise to the solution with 4-methyl-pyridine, the reaction was stirred at 0° C. for one hour. The reaction was poured into saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtrate and concentrated under reduced pressure. The crude was purified by silica gel column chromatography eluting with ethyl acetate 30% in hexane to give the title compound (1.775 g, 50%).

Workup

  1. stirringthe reaction was stirred at 0° C. for one hour
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate, filtrate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified by silica gel column chromatography
  7. washeluting with ethyl acetate 30% in hexane

Sources & evidence

ORD record
ord-be60a6c0d40247b9b655f8894445b6ce
Source dataset
uspto-grants-2013_09
Patent number
US08541575B2

Linked notes

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