p-Toluenesulfonic acid → 6-(4-Bromo-2-fluoro-phenyl)-4,5-difluoro-6,8-dihydro-imidazo[4',5':3,4]benzo[1,2-d]oxazol-7-one

HRID 1914878Notes

Reaction equation

HRID 1914878 reaction equation
[NH2:1][C:2]1[C:19]([F:20])=[C:18]([F:21])[C:5]2[N:6]([C:10]3[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][C:11]=3[F:17])[C:7](=[O:9])[NH:8][C:4]=2[C:3]=1[OH:22].[CH:23](OCC)(OCC)OCC.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[Br:16][C:13]1[CH:14]=[CH:15][C:10]([N:6]2[C:5]3[C:18]([F:21])=[C:19]([F:20])[C:2]4[N:1]=[CH:23][O:22][C:3]=4[C:4]=3[NH:8][C:7]2=[O:9])=[C:11]([F:17])[CH:12]=1

Participants

4

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 31214Ethyl orthoformateHCID 683137725-Amino-1-(4-bromo-2-fluoro-phenyl)-6,7-difluoro-4-hydroxy-1,3-dihydro-benzoimidazol-2-one

Product 1

HCID 672366336-(4-Bromo-2-fluoro-phenyl)-4,5-difluoro-6,8-dihydro-imidazo[4',5':3,4]benzo[1,2-d]oxazol-7-oneYield 65%

Procedure

Intermediate I-16a was prepared from 5-amino-1-(4-bromo-2-fluoro-phenyl)-6,7-difluoro-4-hydroxy-1,3-dihydro-benzoimidazol-2-one (I-14a: 800 mg, 2.14 mmol), triethyl orthoformate (3.7 mL) and p-toluene sulfonic acid (80 mg) using procedures analogous to those used to prepare Intermediate I-15a above to afford 550 mg of the product (65% yield). H1NMR (DMSO-d6, 300 MHz): δ 12.50 (s, 1H), 8.80 (s 1H), 7.97 (d, 1H), 7.65-7.55 (m, 2H). HPLC: 95.7%

Workup

  1. customto prepare Intermediate I-15a above

Sources & evidence

ORD record
ord-b339d34e6b10413196202d808aef5bdd
Source dataset
uspto-grants-2013_12
Patent number
US08614239B2

Reaction notes

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