Hydrogen Bromide → 6-Bromo-1-(3-fluoro-4-hydroxyphenyl)-1H-indazol-4-ol

HRID 2423099Notes

Reaction equation

Br.[Br:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[N:8][N:9]2[C:12]2[CH:17]=[CH:16][C:15]([O:18]CC3C=CC=CC=3)=[C:14]([F:26])[CH:13]=2)=[C:5]([O:27]C)[CH:4]=1.[OH-].[Na+]>C(OCC)(=O)C.O>[Br:2][C:3]1[CH:4]=[C:5]([OH:27])[C:6]2[CH:7]=[N:8][N:9]([C:12]3[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([F:26])[CH:13]=3)[C:10]=2[CH:11]=1

Participants

Conditions

Temperature: 130 °C

Procedure

48% Hydrobromic acid (10 mL) was added to 6-bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-(methyloxy)-1H-indazole (D9) (1.16 g, 2.71 mmol) and the mixture heated at 130° C. for 3 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate and water. The pH was adjusted to 7 by the addition of 2M aqueous sodium hydroxide solution. After separation of the organic layer, the aqueous phase was re-extracted with ethyl acetate. The combined organic layers were dried over magnesium sulphate, filtered and concentrated. The crude product was purified by silica gel chromatography eluting with 5-100% ethyl acetate in hexane. The product was further purified by MDAP to yield the title compound (E5) (170 mg).

Workup

temperatureAfter cooling to room temperature
customAfter separation of the organic layer
extractionthe aqueous phase was re-extracted with ethyl acetate
dry with materialThe combined organic layers were dried over magnesium sulphate
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by silica gel chromatography
washeluting with 5-100% ethyl acetate in hexane
customThe product was further purified by MDAP

Sources & evidence

ORD record: ord-bf242b3131a74e13a0c0e69be5b8974e
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07960563B2

Reaction notes

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