1-Chloro-4-isocyanato-2-(trifluoromethyl) benzene → Sorafenib

HRID 1645376Notes

Reaction equation

HRID 1645376 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH:15][CH3:16])=[O:14])[CH:8]=2)=[CH:4][CH:3]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]=[C:27]=[O:28])=[CH:22][C:21]=1[C:29]([F:32])([F:31])[F:30]>C(OCC)(=O)C>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:1][C:2]2[CH:18]=[CH:17][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([C:13]([NH:15][CH3:16])=[O:14])[CH:8]=3)=[CH:4][CH:3]=2)=[O:28])=[CH:22][C:21]=1[C:29]([F:30])([F:31])[F:32]

Participants

4

Reactant 2

HCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 166551294-(4-Aminophenoxy)-N-methylpicolinamide

Product 1

HCID 216239Sorafenib

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

4-(4-Aminophenoxy)-N-methyl-2-pyridinecarboxamide (52.3 kg, 215 mol) is suspended in ethyl acetate (146 kg) and the suspension is heated to approx. 40° C. 4-Chloro-3-trifluoromethylphenyl isocyanate (50 kg, 226 mol), dissolved in ethyl acetate (58 kg), is then added to such a degree that the temperature is kept below 60° C. After cooling to 20° C. within 1 h, the mixture is stirred for a further 30 min and the product is filtered off. After washing with ethyl acetate (30 kg), the product is dried under reduced pressure (50° C., 80 mbar). 93 kg (93% of theory) of the title compound are obtained as colorless to slightly brownish crystals.

Workup

  1. additionis then added to such a degree that the temperature
  2. customis kept below 60° C
  3. temperatureAfter cooling to 20° C. within 1 h
  4. filtrationthe product is filtered off
  5. washAfter washing with ethyl acetate (30 kg)
  6. customthe product is dried under reduced pressure (50° C., 80 mbar)

Sources & evidence

ORD record
ord-4e52ee5c80b54e6b824d421e30d6820a
Source dataset
uspto-grants-2012_02
Patent number
US08124782B2

Reaction notes

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