Water → Erlotinib

HRID 1184634Notes

Reaction equation

HRID 1184634 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:20]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[C:26]([C:28]#[CH:29])[CH:27]=3)=[N:19][CH:18]=[N:17][C:9]2=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][O:15][CH3:16].Cl.O.[OH-].[Na+]>C(OCC)(=O)C>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:20]([NH:21][C:22]3[CH:23]=[CH:24][CH:25]=[C:26]([C:28]#[CH:29])[CH:27]=3)=[N:19][CH:18]=[N:17][C:9]2=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][O:15][CH3:16]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 176871Erlotinib Hydrochloride

Product 1

HCID 176870ErlotinibYield 98.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Crude erlotinib hydrochloride (100 gm, obtained in reference example 1), water (400 ml) and ethyl acetate (1600 ml) are taken into a reaction flask at 25-30° C. and start stirring. The contents are heated to 60° C., pH of the mass is adjusted to 9 to 10 by adding sodium hydroxide solution (30-40 ml) at 60-65° C. and then stirred for 30-35 minutes at 60-65° C. Separated the layers at 60-65° C., the organic layer is dried with sodium sulfate and then distilled off the solvent completely under vacuum at 50° C. The residue is cooled to 25-30° C., n-heptane (800 ml) is added and the stirred for 45 minutes to 1 hour at 25-30° C. Filtered the compound, washed with n-heptane (200 ml) and then dried at 60-65° C. to give 90 gm of anhydrous erlotinib free base (HPLC Purity: 99.1%, Moisture Content: 0.1%).

Workup

  1. stirringstirred for 30-35 minutes at 60-65° C
  2. customSeparated the layers at 60-65° C.
  3. dry with materialthe organic layer is dried with sodium sulfate
  4. distillationdistilled off the solvent completely under vacuum at 50° C
  5. temperatureThe residue is cooled to 25-30° C.
  6. additionn-heptane (800 ml) is added
  7. stirringthe stirred for 45 minutes to 1 hour at 25-30° C
  8. filtrationFiltered the compound
  9. washwashed with n-heptane (200 ml)
  10. customdried at 60-65° C.

Sources & evidence

ORD record
ord-52b6e4061da948909f4ab92a0e887ad8
Source dataset
uspto-grants-2014_03
Patent number
US08669265B2

Reaction notes

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