Hydrochloric Acid → Erlotinib Hydrochloride

HRID 1942259Notes

Reaction equation

HRID 1942259 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].[ClH:30]>CS(C)=O>[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].[ClH:30]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 176870Erlotinib

Product 1

HCID 176871Erlotinib HydrochlorideYield 0.02%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
27.5 °C

Procedure

Crude erlotinib free base (10 gm, HPLC purity: 98.2%; Content of N-methoxyethyl impurity: 0.24%) is dissolved in dimethylsulfoxide (50 ml) at 25-30° C., to the solution is added 15% methanolic HCl (100 ml) at 25-30° C. while the pH of the mass is adjusted to 2 and then stirred for 30-40 minutes at 25-30° C. The material is filtered, washed with a mixture of dimethyl sulfoxide (10 ml) and methanol (20 ml), and then the material is dried at 60-65° C. under vacuum for 5 hours to give 8.9 gm of pure erlotinib hydrochloride [HPLC purity: 99.92%; Content of N-methoxyethyl impurity: 0.02% (at 1.14 RRT)].

Workup

  1. filtrationThe material is filtered
  2. washwashed with a mixture of dimethyl sulfoxide (10 ml) and methanol (20 ml)
  3. customthe material is dried at 60-65° C. under vacuum for 5 hours

Sources & evidence

ORD record
ord-3d61a65de5c3458385c68fac63b89948
Source dataset
uspto-grants-2013_03
Patent number
US08389531B2

Reaction notes

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