Isopropyl Acetate → Erlotinib Hydrochloride

HRID 1184637Notes

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].C(OC(C)C)(=O)C.[ClH:37].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].[ClH:37]

Participants

Reactant 3

HCID 7915Isopropyl Acetate

HCID 176870Erlotinib

HCID 21866389Hydrogen chloride-ethyl acetate

Product 1

HCID 176871Erlotinib Hydrochloride

Conditions

Temperature: 27.5 °C

Procedure

Erlotinib free base (10 gm) is added to isopropyl acetate (400 ml) under stirring at 25-30° C., the contents are heated to 60° C. and then stirred at 60-65° C. to form a clear solution. To the solution slowly added 7% ethyl acetate HCl (40 ml) at 60-65° C. and stirred for 2 hours at 60-65° C. The resulting mass is slowly cooled to 25-30° C. and then stirred for 1 hour. Filtered the mass, washed with the mixture of isopropyl acetate (40 ml) and ethyl acetate (4 ml) and then dried at 50-55° C. to give 9.9 gm of erlotinib hydrochloride crystalline polymorph form A having polymorph form B undetected [HPLC Purity: 99.89%; to Moisture Content: 0.15%; Mean particle size (D50): 5.48 μm and 90 volume-% of the particles (D90): 18.96 μm].

Workup

temperaturethe contents are heated to 60° C.
stirringstirred at 60-65° C.
customto form a clear solution
temperatureThe resulting mass is slowly cooled to 25-30° C.
stirringstirred for 1 hour
filtrationFiltered the mass
washwashed with the mixture of isopropyl acetate (40 ml) and ethyl acetate (4 ml)
customdried at 50-55° C.

Sources & evidence

ORD record: ord-906be36e24764c4798a7333c2986f66a
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669265B2

Reaction notes

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