Ammonium Chloride → (S)-1-[2-(2-bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

HRID 1691787Notes

Reaction equation

HRID 1691787 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:13][C:12](=[O:14])[CH:11]=[CH:10][NH:9]2)=[CH:4][CH:3]=1.C([Li])CCC.[Br:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH:30]([F:32])[F:31])=[CH:23][C:22]=1[CH2:33][C:34](Cl)=[O:35].[Cl-].[NH4+]>C1COCC1>[Br:20][C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH:30]([F:32])[F:31])=[CH:23][C:22]=1[CH2:33][C:34]([N:9]1[CH:10]=[CH:11][C:12](=[O:14])[CH2:13][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)=[O:35]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 59377679(S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-oneHCID 59377702(2-Bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetic acid chlorideHCID 178418339Butyllithium

Product 1

HCID 46830905(S)-1-[2-(2-bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-oneYield 17.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To 108 mg of (S)-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one in 8 ml THF (anhydrous, inhibitor free) at −78° C. under argon was added 0.18 ml of 2.5 M n-butyl lithium in hexanes. The mixture was stirred at −78° C. for 10 minutes and then 118 mg of (2-bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetic acid chloride dissolved in 2 ml THF was added. The solution was stirred at −78° C. for 30 minutes, then allowed to warm to room temperature for 30 minutes with stirring. To this mixture was then added 10 ml saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate, the organic layer was dried over sodium sulfate, filtered and the solvent was removed in vacuo. Chromatography (20% Ethyl acetate in hexanes) gave 30 mg (S)-1-[2-(2-bromo-5-difluoromethoxy-4-methoxy-phenyl)-acetyl]-2-(4-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one. MS (M+1) 485.

Workup

  1. additionwas added
  2. stirringThe solution was stirred at −78° C. for 30 minutes
  3. temperatureto warm to room temperature for 30 minutes
  4. stirringwith stirring
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialthe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-adaf8f704cf54cfd8061aa9c74934f8f
Source dataset
uspto-grants-2012_04
Patent number
US08153808B2

Reaction notes

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