5'-CHLORO-2'-HYDROXY-4'-METHYL-3'-NITROACETOPHENONE synthesis

Yield:288401-07-0 62%

Reaction Conditions:

with sulfuric acid;sodium nitrite at 0; for 0.5 h;

Steps:

51.1 Step 1: 1- (5-chloro-2-hydroxy-4-methyl-3-nitrophenyl) ethan-1-one (51-1)

To a solution of 1- (5-chloro-2-hydroxy-4-methylphenyl) ethan-1-one (1 g, 5.42 mmol) in H ₂SO ₄ (5 mL) was added NaNO ₂ (690 mg, 8.12 mmol) at 0 . The reaction mixture was stirred at 0 for 0.5 hr. The reaction mixture was poured into ice, the resulting aqueous layer was extracted with ethyl acetate (250 mL x 2) . The organic layer was washed with brine (100 mL) and dried over Na ₂SO ₄. The solvent was evaporated to dryness. The residue was purified with column chromatography on silica gel (petroleum ether: ethyl acetate =10: 1) to obtain the desired compound as yellow solid (770 mg in 62%yield) . ¹H NMR (400 MHz, CDCl ₃) δ 12.60 (s, 1H) , 7.84 (s, 1H) , 2.66 (s, 3H) , 2.38 (s, 3H) . MS (ESI) m/e (M+1) ⁺ 230.0.

References:

WO2018/103688,2018,A1 Location in patent:Paragraph 0530