Hydrochloric Acid → Erlotinib Hydrochloride

HRID 1016389Notes

Reaction equation

HRID 1016389 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:15]=1[O:16][CH2:17][CH2:18][O:19][CH3:20])[N:12]=[CH:11][N:10]=[C:9]2[NH:21][C:22]1[CH:23]=[C:24]([C:28]#[C:29]C(C)(O)C)[CH:25]=[CH:26][CH:27]=1.[OH-].[Na+].[ClH:36]>CC(O)C>[ClH:36].[C:28]([C:24]1[CH:23]=[C:22]([NH:21][C:9]2[C:8]3[C:13](=[CH:14][C:15]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[C:6]([O:5][CH2:4][CH2:3][O:2][CH3:1])[CH:7]=3)[N:12]=[CH:11][N:10]=2)[CH:27]=[CH:26][CH:25]=1)#[CH:29]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 9868438Erlotinib Impurity 14

Product 1

HCID 176871Erlotinib Hydrochloride

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
137.5 °C

Procedure

4-[3-[[6,7-Bis(2-methoxyethoxy]-4-quinazolinyl]amino]phenyl]-2-methyl-3-butyn-2-ol, prepared above (20.0 g, 44.3 mmol), anhydrous solid sodium hydroxide (260 mg, 6.5 mmol) and propan-2-ol (200 mL) were stirred together and heated in a pressure vessel at 135-140° C. for 23 hours. The reaction mixture was cooled to 60-65° C. and concentrated hydrochloric acid (4.8 mL) was added. The resultant mixture was granulated overnight at 20-25° C. to establish crystallization. The mixture was treated with water (10 mL) and stirred at 58-60° C. for 21 hours, cooled to 15-20° C. and granulated for 2 hours. The title product crystals were isolated by filtration, washed with propan-2-ol (2×30 mL) and dried under vacuum at 45-50° C. to remove propan-2-ol. Yield (17.6 g, 92%).

Workup

  1. temperatureThe reaction mixture was cooled to 60-65° C.
  2. customcrystallization
  3. additionThe mixture was treated with water (10 mL)
  4. stirringstirred at 58-60° C. for 21 hours
  5. temperaturecooled to 15-20° C.

Sources & evidence

ORD record
ord-0bacad1d706c49edb9fb8dea8cea0d5f
Source dataset
uspto-grants-2002_11
Patent number
US06476040B1

Reaction notes

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