반응 #40529

ord-8f1b7bacbef04f158bc05613acb1e601

반응 조건

온도
90°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도After cooling
  2. 2
    농축concentration in vacuo
  3. 3
    기타the residue was purified by chromatography (Silica Gel 0.5% methanol/dichloromethane to 2% methanol/dichloromethane)

실험 절차

To a solution of 2-amino-5-bromo-6-fluoro-3-nitro-benzoic acid methyl ester (1.0 g, 3.4 mmol) in dioxane (25 mL), under nitrogen atmosphere, was added bispinacoladaboron (1.3 g, 5.1 mmol), dichloro[1,1′-bis(diphenylphosphine)ferrocene]palladium (II) dichlormethane adduct (0.125 g, 0.17 mmol), and potassium acetate (1.0 g, 10.2 mmol). The resulting mixture was heated at reflux for 18 hours, cooled to room temperature, diluted with ethyl acetate (50 ml) and filtered through Celite®. The resulting solid was triturated with hexanes (40 ml) three times to afford 0.515 g of 2-amino-6-fluoro-3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester. To a mixture of 2-amino-6-fluoro-3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester in ethylene glycol dimethyl ether (10 ml) was added trifluoro-methanesulfonic acid 1-methyl-2-oxo-1,2-dihydro-pyridin-4-yl ester (0.39 g, 1.5 mmol), lithium chloride (0.25 g, 6.0 mmol), sodium carbonate (1.1 ml, 2.2 mmol of 2M), and tetrakistriphenylphosphine palladium (0.18 g, 0.15 mmol). The resulting mixture was heated to 90° C. and allowed to stir for 18 hours. After cooling and concentration in vacuo, the residue was purified by chromatography (Silica Gel 0.5% methanol/dichloromethane to 2% methanol/dichloromethane) to provide the title compound (0.275 g, 25%). 1H NMR (500 MHz, CDCl3) δ 3.58 (s, 3H), 4.03 (s, 3H), 6.30 (d, 1H), 7.32 (d, 1H), 8.45 (br s, 2H), 8.53 (d, 1H)

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07727992B2uspto-grants-2010_06