Water → Erlotinib

HRID 1942256Notes

Reaction equation

HRID 1942256 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
52.5 °C

Procedure

Crude erlotinib hydrochloride (37 gm, obtained in step-I), water (370 ml) and chloroform (370 ml) are taken into a reaction flask at 25-30° C. and stirring begun. The contents are heated to 50-55° 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 is added chloroform (200 ml) and methanol (60 ml) and stirred for 15 minutes at 50° C. (clear solution observed). The layers are separated at 50° C., the organic layer is washed with water (200 ml) at 50° C. and then the organic layers are combined. To the organic layer is added methanol (60 ml) and then dried over sodium sulfate and the total solvent is distilled under vacuum at 50-55° C. To the residue is added n-heptane (300 ml) and stirred for 30 minutes at 25-30° C. The material, is filtered washed with n-heptane (70 ml) and then the material is dried at 60-65° C. under vacuum for 3 hours 30 minutes to give 34 gm of erlotinib free base [HPLC purity: 98.2%; Content of N-methoxyethyl impurity: 0.24% (at 1.14 RRT)].

Workup

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

Sources & evidence

ORD record
ord-0858ce7069564a21b2d8751c1ec4d943
Source dataset
uspto-grants-2013_03
Patent number
US08389531B2

Reaction notes

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