Calcium Carbonate → Afatinib Impurity 56

HRID 1929787Notes

Reaction equation

HRID 1929787 reaction equation
[CH3:1][N:2]([CH3:9])[CH2:3][C:4]#[C:5][C:6]([OH:8])=[O:7].C(=O)([O-])[O-].[Ca+2]>C(OCC)(=O)C.CO>[CH3:1][N:2]([CH3:9])[CH2:3]/[CH:4]=[CH:5]\[C:6]([OH:8])=[O:7]

Participants

5

Reactant 2

HCID 10112Calcium CarbonateHCID 15079752HCID 15079752, compound

Product 1

HCID 59504961Afatinib Impurity 56Yield 39.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

2 g of the compound obtained in step 1) was diluted with 120 ml of a mixed solvent of ethyl acetate and methanol (1:1), and 450 mg of calcium carbonate on palladium was added thereto. The resulting mixture was stirred under a hydrogen gas for two hours. After the reaction terminated, the resulting solution was filtered through a cellite pad and distilled under a reduced pressure. The resulting residue was purified by column chromatography (methylene chloride:methanol=2:1) to obtain the title compound (800 mg, 39%).

Workup

  1. additionwas added
  2. customAfter the reaction terminated
  3. filtrationthe resulting solution was filtered through a cellite pad
  4. distillationdistilled under a reduced pressure
  5. customThe resulting residue was purified by column chromatography (methylene chloride:methanol=2:1)

Sources & evidence

ORD record
ord-e45c468293b94d2e840300a46cbb77cd
Source dataset
uspto-grants-2012_05
Patent number
US08188102B2

Reaction notes

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