Potassium Hydroxide → ethyl 4-bromo-3-methoxy-1H-indazole-1-carboxylate

HRID 1716730Notes

Reaction equation

[OH-].[K+].N([CH2:5]NC(N)=O)=O.[CH2:10]([O:12][C:13]([N:15]1[C:23]2[C:18](=[C:19]([Br:24])[CH:20]=[CH:21][CH:22]=2)[C:17]([OH:25])=[N:16]1)=[O:14])[CH3:11]>CCOCC.C1COCC1>[CH2:10]([O:12][C:13]([N:15]1[C:23]2[C:18](=[C:19]([Br:24])[CH:20]=[CH:21][CH:22]=2)[C:17]([O:25][CH3:5])=[N:16]1)=[O:14])[CH3:11]

Participants

Conditions

Temperature: -78 °C

Procedure

To a 0° C. mixture of KOH (50% in H2O, 50 ml) and Et2O (150 ml), N-nitrosomethylurea (10.7 g, 103 mmol) was added portionwise over 40 minute period. After stirring for additional 20 minutes, the mixture was cooled to −78° C. and the upper bright yellow layer was poured into a 0° C. suspension of 4-Bromo-3-hydroxy-indazole-1-carboxylic acid ethyl ester CLXXXIV (2.96 g, 10.4 mmol) in a mixture of Et2O (100 ml) and THF (30 ml). After 2 hours, the yellow solution was warmed to room temperature and was left to stand at room temperature for 24 hours. The mixture was then washed with H2O and brine. The organic layer was dried over MgSO4, filtered, concentrated, and purified via flash chromatography (hexane/EtOAc) affording 4-Bromo-3-methoxy-indazole-1-carboxylic acid ethyl ester CLXXXV as an off-white solid (40% yield).

Workup

additionwas added portionwise over 40 minute period
additionthe upper bright yellow layer was poured into a 0° C.
waitAfter 2 hours
temperaturethe yellow solution was warmed to room temperature
waitwas left
waitto stand at room temperature for 24 hours
washThe mixture was then washed with H2O and brine
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated
custompurified via flash chromatography (hexane/EtOAc)

Sources & evidence

ORD record: ord-2cf0ca92886f4f1fb79f7f6537f6b7a0
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07803830B2

Reaction notes

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