Isopropyl iodide → Ethyl 5-fluoro-1-isopropyl-1H-indazole-3-carboxylate

HRID 602479Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]([O:13][CH2:14][CH3:15])=[O:12].[CH3:16][C:17](C)([O-])[CH3:18].[K+].IC(C)C>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:17]([CH3:18])[CH3:16])[N:6]=[C:5]2[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of ethyl 5-fluoro-1H-indazole-3-carboxylate (487 mg, 2.3 mmol, J. Heterocycl. Chem. 1964, 1, 239-241) in tetrahydrofuran (4 mL) was added potassium tert-butoxide (289 mg, 2.57 mmol) at 0° C. After stirring at 0° C. for 1 h, 2-iodopropane (438 mg, 2.57 mmol) was added to the mixture. The resulting mixture was stirred at room temperature for 20 h and concentrated under reduced pressure. The mixture was diluted with ethyl acetate (50 mL), washed with water (30 mL) and brine (30 mL). The organic layer was separated, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (10:1 to 2:1) to give 205 mg (35%) of the title compound as a yellow crystal.

Workup

stirringThe resulting mixture was stirred at room temperature for 20 h
concentrationconcentrated under reduced pressure
additionThe mixture was diluted with ethyl acetate (50 mL)
washwashed with water (30 mL) and brine (30 mL)
customThe organic layer was separated
dry with materialdried over magnesium sulfate
concentrationconcentrated under reduced pressure
customThe resulting residue was chromatographed on a column of silica gel eluting with n-hexane/ethyl acetate (10:1 to 2:1)

Sources & evidence

ORD record: ord-5de1ff1ecfd14f49a76de2612b6b71c6
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07906532B2

Reaction notes

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