Salicylamide → 2-(2-Hydroxyphenyl)-4H-1,3-benzoxazin-4-one

HRID 1475613Notes

Reaction equation

[CH:1]1[CH:2]=[CH:3][C:4]([OH:28])=[C:5]([C:7]2[N:8]=[C:9]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=3[OH:27])N(C3C=CC(C(O)=O)=CC=3)N=2)[CH:6]=1.C(Cl)(=O)C1C(=CC=CC=1)[OH:32].C(N)(=O)C1C(=CC=CC=1)O>>[OH:28][C:4]1[CH:3]=[CH:2][CH:1]=[CH:6][C:5]=1[C:7]1[O:27][C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:9](=[O:32])[N:8]=1

Participants

Reactant 3

HCID 5147Salicylamide

HCID 74041Salicyloyl chloride

HCID 214348Deferasirox

Product 1

HCID 1356857232-(2-Hydroxyphenyl)-4H-1,3-benzoxazin-4-one

Procedure

U.S. Pat. No. 6,465,504 discloses a process for preparing Deferasirox wherein the process includes reacting salicyloyl chloride with salicylamide at 170° C. to obtain 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one, and further crystallization in ethanol to obtain slight yellow color crystals of 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one. 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one which is further reacted with 4-hydrazinebenzoic acid in presence of ethanol to give Deferasirox. Major drawback of this process is preparation of 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one at high temperature and in the absence of solvent which causes formation of several impurities which is difficult to avoid.

Workup

customat 170° C.
customto obtain
custom2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one, and further crystallization in ethanol

Sources & evidence

ORD record: ord-3511eb47eeac486bb5f425ef0f7aa513
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018389B2

Reaction notes

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