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ChemicalBook CAS DataBase List METHYL 6-BROMO-1H-INDAZOLE-3-CARBOXYLATE
885278-42-2

METHYL 6-BROMO-1H-INDAZOLE-3-CARBOXYLATE synthesis

4synthesis methods
-

Yield:885278-42-2 76%

Reaction Conditions:

with sulfuric acid at 90; for 4 h;

Steps:

A

To a suspension of 6-bromo-1H-indazole-3-carboxylic acid (3.00 g, 12 mmol) in methanol (50 mL, 1 mol) was added Sulfuric acid (1.50 mL, 28 mmol), and the mixture was heated to 90 °C for 4 hours. After cooling to rt, the mixture was diluted with 200 mL EtOAc, and washed with 150 mL sat. NaHC0 2 (aq) and 150 mL brine. The organic extracts were dried (Na 2 S0 4 ) and concentrated in vacuo to provide 2.42 g (76%) of pure 6-bromo-lH-indazole-3-carboxylic acid methyl ester as a yellow solid. This material was diluted in tetrahydrofuran (50 mL), cooled to 0 °C, then sodium hydride (0.417 g, 10.4 mmol) was added. The mixture was stirred at 0 °C for 30 minutes, then [β-(trimethylsilyl)ethoxy]methyl chloride (1.85 mL, 10.4 mmol) was added dropwise. The mixture was allowed to slowly warm to room temperature over 90 minutes, then MeOH was added to quench excess hydride, and the mixture was concentrated in vacuo. The residue was diluted with 200 mL EtOAc, then washed with 200 mL brine. The aqueous layer was further extracted with 50 mL EtOAc, then the combined organic extracts were dried (Na2SO4 ) and concentrated in vacuo. Purification by CombiFlash (40 g column; load with CH2Cl2 ; 100:0 to 50:50 heptane:EtOAc over 30 minutes) provided 3.22 g (88%) of the title compound as a yellow oil.

References:

WO2013/24011,2013,A1 Location in patent:Page/Page column 51

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