Pyridine → HCID 24872412, compound

HRID 2241921Notes

Reaction equation

HRID 2241921 reaction equation
C([O:4][C:5]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:6]=1[C:7]([OH:9])=O)(=O)C.P(Cl)(Cl)(Cl)=O.N1C=CC=CC=1.[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:38][CH2:37][N:36](C(=O)C)[CH2:35][CH2:34]2)=[C:29]([F:42])[CH:28]=1.C(=O)([O-])O.[Na+].[OH-].[Na+]>O1CCCC1.O>[Cl:14][C:11]1[CH:12]=[CH:13][C:5]([OH:4])=[C:6]([CH:10]=1)[C:7]([NH:26][C:27]1[CH:32]=[CH:31][C:30]([N:33]2[CH2:34][CH2:35][NH:36][CH2:37][CH2:38]2)=[C:29]([F:42])[CH:28]=1)=[O:9]

Participants

9

Reactant 6

HCID 1049PyridineHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 28208132-(Acetyloxy)-5-chlorobenzoic acidHCID 28972592HCID 28972592, compound

Product 1

HCID 24872412HCID 24872412, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Acetoxy-5-chlorobenzoic acid (0.257 g, 1.20 mmol), phosphorus oxychloride (0.184 g, 1.20 mmol) and pyridine (0.095 g, 1.20 mmol) were added to a solution of 1-[4-(4-amino-2-fluorophenyl)piperazin-1-yl]ethanone (compound of Reference Example 85; 0.237 g, 1.00 mmol) in tetrahydrofuran (3 ml) under ice cooling, and the mixture was stirred under ice cooling for 3 hours. The reaction mixture was neutralized by addition of saturated aqueous sodium hydrogencarbonate, diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. 6N Hydrochloric acid (6 ml) was added to the residue obtained by evaporation of the solvent under reduced pressure, and the mixture was refluxed for 5 hours. The reaction mixture was cooled to room temperature and neutralized by addition of 2N aqueous sodium hydroxide. The precipitated solid was collected by filtration, washed with water, and purified by column chromatography on silica gel (methanol:chloroform=1:10) to give the title compound (0.017 g, 5%) as a yellow solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over sodium sulfate
  4. addition6N Hydrochloric acid (6 ml) was added to the residue
  5. customobtained by evaporation of the solvent under reduced pressure
  6. temperaturethe mixture was refluxed for 5 hours
  7. filtrationThe precipitated solid was collected by filtration
  8. washwashed with water
  9. custompurified by column chromatography on silica gel (methanol:chloroform=1:10)

Sources & evidence

ORD record
ord-d2cc4acb3d194e41bccff18dac1da3ee
Source dataset
uspto-grants-2010_03
Patent number
US07671058B2

Reaction notes

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