ETHYL 2-(3-FLUORO-4-NITROPHENYL)PROPIONATE synthesis

Yield: 96%

Reaction Conditions:

with potassium tert-butylate in N,N-dimethyl-formamide at -45; for 0.25 h;Inert atmosphere;

Steps:

1 Synthesis of example C1 : N-[[2-(3-Chlorophenyl)-5-(trifluoromethyl)-2H-pyrazol-3-yl]- methyl]-2-[4-(1 ,1 -dioxo-[1 ,2]thiazolidin-2-yl)-3-fluoro-phenyl]-propionamide Stepl :
Under a nitrogen atmosphere, potassium tert. butyloxide (8.2 g, 73 mmol) was slurried in DMF and cooled to -45 °C. A mixture of o-fluoronitrobenzene (3.88 mL, 36.6 mmol) and ethyl-2-chloropropionate (4.66 mL, 36.6 mmol) was added while maintaining this temperature and the mixture was stirred for 15 min. The reaction mixture was adjusted with HCI (16%) to pH = 4 and diluted with water (250 mL). The aqueous phase was repeatedly extracted with ethyl acetate (3 x 100 mL), the combined organic phases are washed with water (3 x 100 mL) and brine (1 x 100 mL) and dried over magnesium sulfate. After concentration in vacuo ethyl 2-(3-fluoro-4-nitrophenyl)propanoate was obtained (8.47 g, 96 %).

References:

GRÜNENTHAL GMBH;FRANK, Robert;CHRISTOPH, Thomas;DAMANN, Nils;LESCH, Bernhard;BAHRENBERG, Gregor;SAUNDERS, Derek, John;STOCKHAUSEN, Hannelore;KIM, Yong-Soo;KIM, Myeong-Seop;LEE, Jeewoo WO2013/68463, 2013, A1 Location in patent:Page/Page column 56