Triethylamine → HCID 69355097, compound

HRID 1836357Notes

Reaction equation

HRID 1836357 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([Cl:6])=[O:5].Cl.Cl.[NH2:14][C:15]1[CH:16]=[C:17]([CH:27]=[CH:28][CH:29]=1)[C:18]([CH:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1)=[O:19].NC1C=C(C=CC=1)C(C1CCN(C)CC1)=O.C(N(CC)CC)C>C(OCC)(=O)C.[OH-].[Na+].O1CCCC1.C(Cl)Cl.CO.[OH-].[NH4+]>[ClH:6].[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:14][C:15]1[CH:16]=[C:17]([CH:27]=[CH:28][CH:29]=1)[C:18]([CH:20]1[CH2:21][CH2:22][N:23]([CH3:26])[CH2:24][CH2:25]1)=[O:19])=[O:5]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 5880812,4-Difluorobenzoyl chloride2×HCID 101306514-[3-Aminobenzoyl]-1-methylpiperidineHCID 23499410HCID 23499410, compound

Product 1

HCID 69355097HCID 69355097, compoundYield 81%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×HCID 14798Sodium HydroxideSolvent3×HCID 21896990Dichloromethane methanol ammonium hydroxideSolvent

Procedure

2,4 difluorobenzoyl chloride (100 μl, 0.82 mmol) was added to a mixture of 4-[3-aminobenzoyl]-1-methylpiperidine dihydrochloride (200 mg, 0.69 mmol), tetrahydrofuran (5 ml) and 1N sodium hydroxide solution (2.4 ml). The reaction mixture was stirred 24 h at room temperature. The reaction mixture was diluted with ethyl acetate and 1N sodium hydroxide solution then extracted with ethyl acetate. The ethyl acetate extracts were washed with brine, then dried over sodium sulfate. Solvent was removed under reduced pressure to give 220 mg. This mixture contained product and unreacted 4-[3-aminobenzoyl]-1-methylpiperidine. This mixture was dissolved in tetrahydrofuran and triethylamine (144 μl, 1.03 mmol) was added to the solution followed by 2,4 difluorobenzoyl chloride (100 μl, 0.82 mmol). The resulting mixture was stirred for 2 h at room temperature. The reaction mixture was diluted with ethyl acetate and 1N sodium hydroxide solution then extracted with ethyl acetate. The ethyl acetate extracts were washed with 1N sodium hydroxide solution, water, brine, then dried over sodium sulfate. Solvent was removed under reduced pressure to give an oil. The oil was dissolved in methylene chloride:methanol:ammonium hydroxide (100:5:0.5) and the resulting precipitate was filtered and discarded. Purification by radial chromatography (silica gel, 1000 micron rotor, methylene chloride:methanol:ammonium hydroxide, 100:5:0.5) gave 200 mg (81%) of a clear colorless oil. Crystallization as the hydrochloric acid salt from ethyl acetate/ethanol provided 185 mg of a white powder.

Workup

  1. extractionthen extracted with ethyl acetate
  2. washThe ethyl acetate extracts were washed with brine
  3. dry with materialdried over sodium sulfate
  4. customSolvent was removed under reduced pressure
  5. customto give 220 mg
  6. stirringThe resulting mixture was stirred for 2 h at room temperature
  7. extractionthen extracted with ethyl acetate
  8. washThe ethyl acetate extracts were washed with 1N sodium hydroxide solution, water, brine
  9. dry with materialdried over sodium sulfate
  10. customSolvent was removed under reduced pressure
  11. customto give an oil
  12. filtrationthe resulting precipitate was filtered
  13. customPurification by radial chromatography (silica gel, 1000 micron rotor, methylene chloride:methanol:ammonium hydroxide, 100:5:0.5)

Sources & evidence

ORD record
ord-67b3935e57dc42629427d1c848158d18
Source dataset
uspto-grants-2004_08
Patent number
US06777428B1

Reaction notes

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