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778611-16-8

3-TERT-BUTYL-1-(4-FLUOROPHENYL)-1H-PYRAZOL-5-AMINE synthesis

2synthesis methods
59997-51-2 Synthesis
Pivaloylacetonitrile

59997-51-2
270 suppliers
$6.00/25g

371-14-2 Synthesis
4-FLUOROPHENYLHYDRAZINE

371-14-2
79 suppliers
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Yield:778611-16-8 89%

Reaction Conditions:

Stage #1: trimethylacetylacetonitrile;4-fluorophenylhydrazinewith acetic acid in ethanol; for 18 h;Heating / reflux;
Stage #2: with sodium hydrogencarbonate in ethanol;water;ethyl acetate;

Steps:

4

To a solution of 4,4-dimethyl-3-oxopentanenitrile (7.54 g, 59.7 mmol) and 4- fluorophenylhydrazine (10.0 g, 59.7 mmol) in anhydrous EtOH (100 mL) was added acetic acid (4.8 mL, 83.5 mL) dropwise. The reaction was stirred at reflux under N2 for 18 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between EtOAc (150 mL) and aqueous saturated NaHCOβ solution (100 mL). The organic layer was separated, washed successively with water and brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude residue was purified by MPLC (eluting with 10 to 15% EtOAc/hexanes) to give 12.4 g (89 %) of the desired product. 1H-NMR (DMSO- cfe) δ 7.59-7.53 (m, 2H), 7.30-7.22 (m, 2H), 5.36 (s, 1 H), 5.19 (br s, 2H), 1.19 (s, 9H); LC-MS m/z [M+H]+ 233.9, RT 1.95 min.

References:

WO2007/64872,2007,A2 Location in patent:Page/Page column 74-75

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