ChemicalBook CAS DataBase List 4-BROMO-3-(4-FLUOROPHENYL)-1-METHYL-1H-PYRAZOLE

4-BROMO-3-(4-FLUOROPHENYL)-1-METHYL-1H-PYRAZOLE synthesis

5synthesis methods

Product Name:4-BROMO-3-(4-FLUOROPHENYL)-1-METHYL-1H-PYRAZOLE
CAS Number:863605-34-9
Molecular formula:C10H8BrFN2
Molecular Weight:255.09

474706-36-0 Synthesis

4-Bromo-5-(4-fluorophenyl)-1(2)H-pyrazole

474706-36-0
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$60.00/100mg

74-88-4
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$15.00/10g

4-BROMO-3-(4-FLUOROPHENYL)-1-METHYL-1H-PYRAZOLE

863605-34-9
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Yield:863605-34-9 54.9%

Reaction Conditions:

Stage #1: 4-bromo-3-(4-fluorophenyl)-1H-pyrazolewith sodium hydride in N,N-dimethyl-formamide;mineral oil at 0 - 20;Inert atmosphere;
Stage #2: methyl iodide in N,N-dimethyl-formamide;mineral oil at 0 - 20;

Steps:

Intermediate 2: 4-bromo-3-(4-fluorophenyl)-1-methyl-1H-pyrazole

To a solution of 4-bromo-3 -(4-fluorophenyl)- lH-pyrazole (14.47 g, 60.0 mmol) in DMF (100 mL) was added 60% NaH dispersion in mineral oil (2.88 g, 72.0 mmol) in portions at 0 °C under nitrogen. The reaction mixture was stirred at rt for 30 min. The reaction mixture was cooled to 0 °C and Mel (4.88 mL, 78 mmol) was added slowly. The reaction mixture was stirred at rt for lh and diluted with EtOAc and water. The layers were separated. The aqueous layer was extracted with EtOAc (2 x 40 mL). The combined organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by BIOTAGE (300 g Thomson, 50% CH₂Cl₂/hexane equilibration, 50-80% CH₂Cl₂/hexane, 3 L, then 80-85% 0.7 L) to give Intermediate 2 (8.4 g, 54.9%) as a white solid. MS(ES): m/z= 254.88/256.88 [M+H]⁺. HPLC Ret time (Method B): 3.68 min. NMR (400MHz, chloroform-d) δ 7.92 - 7.82 (m, 2H), 7.47 (s, 1H), 7.13 (t, J=8.8 Hz, 2H), 3.94 (s, 3H).

References:

WO2014/100540,2014,A1 Location in patent:Page/Page column 55-56