METHYL 6-BROMO-1H-INDAZOLE-3-CARBOXYLATE synthesis
- Product Name:METHYL 6-BROMO-1H-INDAZOLE-3-CARBOXYLATE
- CAS Number:885278-42-2
- Molecular formula:C9H7BrN2O2
- Molecular Weight:255.07
67-56-1
660823-36-9
885278-42-2
Concentrated sulfuric acid (1.50 mL, 28 mmol) was slowly added to a methanolic (50 mL, 1 mol) suspension of 6-bromo-1H-indazole-3-carboxylic acid (3.00 g, 12 mmol), and the reaction mixture was heated to 90°C and held for 4 hours. After completion of the reaction, it was cooled to room temperature and the mixture was diluted with 200 mL of ethyl acetate and washed sequentially with 150 mL of saturated aqueous sodium bicarbonate and 150 mL of brine. The organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 2.42 g (76% yield) of methyl 6-bromo-1H-indazole-3-carboxylate as a yellow solid. The product was dissolved in tetrahydrofuran (50 mL), cooled to 0 °C and sodium hydride (0.417 g, 10.4 mmol) was added in batches. After stirring at 0 °C for 30 min, [β-(trimethylmethylsilyl)ethoxy]methyl chloride (1.85 mL, 10.4 mmol) was added slowly and dropwise. The reaction mixture was slowly warmed to room temperature over 90 min, excess sodium hydride was quenched by the addition of methanol and concentrated under reduced pressure. The residue was diluted with 200 mL of ethyl acetate and washed with 200 mL of brine. The aqueous phase was back-extracted with 50 mL of ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Purification by CombiFlash Fast Chromatography System (40g silica gel column; dissolved in dichloromethane; elution gradient: 100:0 to 50:50 heptane:ethyl acetate, 30 min) gave 3.22 g (88% yield) of the target compound as a yellow oil.
67-56-1
789 suppliers
$9.00/25ml
660823-36-9
142 suppliers
$31.00/100mg
885278-42-2
103 suppliers
$73.00/250mg
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
660823-36-9
142 suppliers
$31.00/100mg
885278-42-2
103 suppliers
$73.00/250mg
6326-79-0
276 suppliers
$6.00/1g
885278-42-2
103 suppliers
$73.00/250mg
7099-87-8
55 suppliers
$35.00/100mg
885278-42-2
103 suppliers
$73.00/250mg