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Stage #1: at 20℃; for 2 h; Stage #2: With sodium hydroxide In water; ethyl acetateCooling with ice
Preparation 6 5-iodo-2-methyl-2H-indazole To a solution of 5-iodo-1H-indazole (500 g, 2.05 mol) in EtOAc (4 L) is added trimethyloxonium tetrafluoroborate (450 g, 3.04 mol). After the resulting white suspension is stirred at room temperature for 2 h, it is concentrated under vacuum. Ice water (1 L) is added to the residue, and it is basified to pH 12 with 10percent aqueous NaOH solution. The solids are collected by filtration, and redissolved in DCM (5 L). The insolubles are filtered off and the filtrate is washed with 10percent aqueous NaOH solution (2*100 mL). The organic layer is dried over anhydrous Na2SO4, filtered through a short silica gel column, and concentrated. Methyl tert-butyl ether is added to the residue to give a slurry and the product is collected by filtration to give the title compound (360 g, 68.0percent). MS (m/z): 259.0 (M+H).
1-((4,4-difluorocyclohexyl)methyl)-5-iodo-1H-indazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
32%
With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 16h;
To a stirred solution of 5-iodo-1H-indazole (0.83 g, 5.396 mmol, 0.8 eq) in DMF (15 mL) NaH (0.25 mg, 3.396 mmol, 1.2 eq, 50% by wt) was added at 0 C., followed by the addition of <strong>[858121-94-5]4-(bromomethyl)-1,1-difluorocyclohexane</strong> (0.90 g, 4.245 mmol, 1.0 eq) and the reaction mixture was stirred at ambient temperature for 16 h. After completion of the reaction (monitored by TLC, TLC system 5% MeOH/DCM, Rf-0.4), the reaction mixture was quenched with ice cold water (50 mL), extracted with EtOAc (3×50 mL), washed with brine (50 mL), dried over Na2SO4 and was then concentrated under reduced pressure to get the crude product which was purified by column chromatography (230-400 mesh silica gel; 0 to 3% MeOH-DCM) to separate the two isomers. The major isomer was the desired 1-((4,4-difluorocyclohexyl)methyl)-5-iodo-1H-indazole which was confirmed by 1H-NMR to afford intermediate C7 (0.54 g, 32%).
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