Ammonium Chloride → 1-(2-Chloro-5-fluoro-pyridin-4-yl)-3,3-diphenyl-propan-1-one

HRID 1617480Notes

Reaction equation

HRID 1617480 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([F:9])=[CH:4][N:3]=1.C([Li])CCC.CON(C)[C:18](=[O:33])[CH2:19][CH:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:18](=[O:33])[CH2:19][CH:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:5]([F:9])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 248204952-Chloro-5-fluoro-4-iodopyridineHCID 54293842N-Methoxy-N-methyl-3,3-diphenyl-propionamideHCID 178418339Butyllithium

Product 1

HCID 866609411-(2-Chloro-5-fluoro-pyridin-4-yl)-3,3-diphenyl-propan-1-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

At −70° C. to a solution of 2-chloro-5-fluoro-4-iodopyridine (873 mg) in THF (20 mL) was added n-butyllithium (2.2 mL, 1.6M in hexane) over a period of 15 min slowly. To that solution N-methoxy-N-methyl-3,3-diphenyl-propionamide (200 mg) in THF (8 mL) was added and stirring was continued at that temperature for 1 h. A saturated solution of NH4Cl was added, the mixture was diluted with EtOAc, the phases were separated and the inorganic one was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (CH2Cl2/n-heptane 1:2) to yield the title compound as a white solid, MS (ESI+): m/z=340.09 ([M+H]+, 1Cl).

Workup

  1. customthe phases were separated
  2. extractionthe inorganic one was extracted with EtOAc (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography on silica gel (CH2Cl2/n-heptane 1:2)

Sources & evidence

ORD record
ord-e01b477264bf49959a810bd07dd4a27c
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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