Water → Erlotinib

HRID 1184633Notes

Reaction equation

HRID 1184633 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.C(Cl)(Cl)Cl.[OH-].[Na+]>CO>[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

6

Reactant 4

HCID 962WaterHCID 6212Chloroform2×HCID 14798Sodium HydroxideHCID 176871Erlotinib Hydrochloride

Product 1

HCID 176870ErlotinibYield 100.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
30 °C

Procedure

Crude erlotinib hydrochloride (37 gm, obtained in reference example 1), water (370 ml) and chloroform (370 ml) are taken into a reaction flask at 25-30° C. and start stirring. The contents are heated to 5-55° C., sodium hydroxide solution is added at 50-55° C. and then stirred for 15 minutes at 50° C. (clear solution not observed). To the reaction mass added chloroform (200 ml) and methanol (60 ml) and stirred for 15 minutes at 50° C. (clear solution observed). Separated the layers at 50° C., the organic layer is washed with water (200 ml) at 50° C. and then combined the organic layers. To the organic layer added methanol (60 ml) dried over sodium sulfate and distilled the total solvent under vacuum at 50-55° C. To the residue added n-heptane (300 ml) and stirred for 30 minutes at 25-30° C. Filtered the material, washed with n-heptane (70 ml) and then dried the material at 60-65° C. under vacuum for 3 hours 30 minutes to give 34 gm of anhydrous erlotinib free base (HPLC Purity: 98.2%, Moisture Content: 0.2%).

Workup

  1. stirringstirred for 15 minutes at 50° C. (clear solution not
  2. stirringstirred for 15 minutes at 50° C. (clear solution observed)
  3. customSeparated the layers at 50° C.
  4. washthe organic layer is washed with water (200 ml) at 50° C.
  5. additionTo the organic layer added methanol (60 ml)
  6. dry with materialdried over sodium sulfate
  7. distillationdistilled the total solvent under vacuum at 50-55° C
  8. additionTo the residue added n-heptane (300 ml)
  9. stirringstirred for 30 minutes at 25-30° C
  10. filtrationFiltered the material
  11. washwashed with n-heptane (70 ml)
  12. customdried the material at 60-65° C. under vacuum for 3 hours 30 minutes

Sources & evidence

ORD record
ord-c97f9d8cc1134fdc8d68b406383c367f
Source dataset
uspto-grants-2014_03
Patent number
US08669265B2

Reaction notes

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