1-(Tetrahydropyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester synthesis

3synthesis methods

Product Name:1-(Tetrahydropyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester
CAS Number:903550-26-5
Molecular formula:C14H23BN2O3
Molecular Weight:278.15

76-09-5

1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole

449758-17-2

1-(Tetrahydropyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester

903550-26-5

1. 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (14.1.A, 83 mmol) and 100 mL of anhydrous THF were added to a 500 mL triple-necked flask and dissolved with stirring. 2. The reaction system was cooled to -78 °C (dry ice/acetone bath) and n-butyllithium (1.6 M hexane solution, 52 mL, 83 mmol) was slowly added dropwise, keeping the temperature below -70 °C. The reaction system was cooled to -78 °C (dry ice/acetone bath). 3. After the dropwise addition, the reaction was continued with stirring at -78 °C for 5 min, followed by the addition of pinacolborane (9.8 g, 83 mmol). 4. 4. After keeping the reaction at a low temperature for 5 minutes, slowly add triisopropyl borate (19 g, 103 mmol) dropwise. 5. 5. Control the rate of temperature increase and bring the reaction system to room temperature over 90 minutes. 6. 6. The reaction was continued with stirring for 16 hours at room temperature (TLC to monitor the progress of the reaction). 7. Upon completion of the reaction, the reaction was quenched to pH 7-8 with saturated aqueous NH4Cl. 8. Extracted with ethyl acetate (3 x 50 mL), the organic phases were combined and dried over anhydrous Na2SO4. 9. After concentration under pressure, purification by silica gel column chromatography (eluent: petroleum ether/ethyl acetate gradient elution) afforded the white solid product 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (14.1.B, 7.2 g, 38% yield).

76-09-5 Synthesis

76-09-5
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449758-17-2 Synthesis

449758-17-2
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903550-26-5
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$6.00/1g

Yield:903550-26-5 78%

Reaction Conditions:

Stage #1: 2,3-dimethyl-2,3-butane diol;1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolewith n-butyllithium in tetrahydrofuran;hexanes at -78; for 0.0833333 h;
Stage #2: with Triisopropyl borate in tetrahydrofuran;hexanes at -78 - 20; for 17.5 h;
Stage #3: with water;ammonium chloride in tetrahydrofuran;hexanes; pH=~ 7 - 8;

Steps:

7.14.1

l-(Tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (14.B.A). To a 500ml flask was added l-(tetrahydro-2H-pyran-2-yl)-lH- pyrazole 14.1.A and 100 ml of THF. The solution was cooled to -78 ⁰C at which time butyllithium (52 ml, 83 mmole, 1.6M in hexanes) and pinacol (9.8 g, 83 mmole) were added. The reaction was stired for 5 minutes at -78 C and then triisopropyl borate (19 g, 103 mmole) was added. The reaction was slowly warmed to room temperature over 90 minutes and then stirred at room temperature for an additional 16 hours at which time the reaction was quenched with NH₄Cl aq. (pH ~7-8), extracted with EtOAc, and purified by silica gel chromatography to give l-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-lH-pyrazole 14.1.B (7.2 g, 38% yield).

References:

WO2010/93849,2010,A2 Location in patent:Page/Page column 63

76-09-5 Synthesis

76-09-5
396 suppliers
$10.00/1g