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With sulfuric acid; at 85℃; for 30h;Inert atmosphere;
To the solution of 2-chloro-6- hydroxybenzoic acid (i-2a) (1.71 g, 10 mmol) in CH3OH (100 ml) was added concentrated sulfuric acid (10 ml) drop wise. The mixture solution was protected by N2 and stirred at 85 C for 30 h. the solution was concentrated to be purified by chromatography column (EA:PE=1 :4) to afford 1.5 g product (81%). LCMS (ESI) calc'd [M+H]+: 186.59, found: 187.0.
81%
With sulfuric acid; at 85℃; for 30h;Inert atmosphere;
To the solution of <strong>[56961-31-0]2-chloro-6-hydroxybenzoic acid</strong> (i-2a) (1.71 g, 10 mmol) in CH3OH (100 ml) was added concentrated sulfuric acid (10 ml) drop wise. The mixture solution was protected by N2 and stirred at 85 C for 30 h. The solution was concentrated and purified by chromatography column(EA:PE=1:4) to afford 1.5 g product (8 1%). LCMS (ESI) calc?d [M+H]: 186.59, found:187.0.
2-chloro-6-(2-(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yloxy)acetoxy)benzoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20.0℃; for 12.0h;
General procedure: A solution of compound 3, substituted methyl salicylate (4a-4t), 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (EDC.HCl), N-Hydroxybenzotriazole (HOBt) and 4-dimethylaminopyridine (DMAP) in DMF (50 mL) was stirred for 12 h at room temperature. Then, compounds 5a-5t were obtained by subsequent purification with flash chromatography (acetate: petroleum ether = 1:5-1:2).
With caesium carbonate; In N,N-dimethyl acetamide; at 150.0℃; for 24.0h;Inert atmosphere;
The mixture of i- 2b (186 mg, lmmol), bromocyclopropane (1.2 g, 10.0 mmol), Cs2C03 (414 mg, 3.0 mmol), DM AC (15 ml) was protected by N2 and stirred at 150 C for 24 h. Then the solution was filtered and concentrated to be purified by chromatography column (EA: PE =1 :4) to afford 198 mg product (87%). LCMS (ESI) calc'd [M+H]+: 226.66, found: 227.1.
87%
With caesium carbonate; In N,N-dimethyl acetamide; at 150.0℃; for 24.0h;Inert atmosphere;
The mixture of i-2b(186 mg, lmmol), bromocyclopropane (1.2 g, 10.0 mmol), Cs2CO3 (414 mg, 3.0 mmol),DMAC (15 ml) was protected by N2 and stirred at 150 C for 24 h. Then the reaction mixture was filtered, concentrated, and purified by chromatography column (EA: PE =1:4) to afford 198 mg product (87%). LCMS (ESI) calc?d [M+H]: 226.66, found: 227.1.
With potassium carbonate; In N,N-dimethyl-formamide; at 20.0℃;Cooling with ice;
Production Example 9-1 Methyl 2-chloro-6-(methoxymethyl)benzoate To a mixture of <strong>[176750-70-2]methyl 2-chloro-6-hydroxybenzoate</strong> (970 mg, 5,2 mmol) and N,N-dimethylformamide (10 mL) were sequentially added potassium carbonate (1.1 g, 7.8 mmol) and methoxymethyl chloride (0.41 mL, 5.4 mmol) under ice cooling and the resultant was stirred at room temperature for 3 hours. Potassium carbonate (0.36 g, 2.6 mmol) and methoxymethyl chloride (0.20 mL, 2.6 mmol) were sequentially added to the reaction mixture under ice cooling and the resultant was stirred overnight at room temperature. Water was added to the reaction mixture and the resultant was extracted with ethyl acetate. The organic layer was washed sequentially with water and brine and evaporated to remove the solvent under a reduced pressure. The residue was purified by filtration through NH silica gel to give the title compound (1.2 g, 97% yield). 1H-NMR Spectrum (CDCl3) delta (ppm): 3.47 (s, 3H) 3.46-3.48 (m, 3 H)3.95 (s, 3H) 5.19 (s, 2 H) 7.03-7.06 (m, 1 H) 7.06 -7.09 (m, 1 H) 7.24 -7.29 (m, 1 H).
Multi-step reaction with 4 steps
1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 50 °C
2: sodium hydroxide / methanol / 2 h / 20 °C
3: pyridine / 16 h / 140 °C
4: hydrogenchloride / methanol / 2 h / 100 °C
Multi-step reaction with 4 steps
1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 50 °C
2: sodium hydroxide; lithium hydroxide monohydrate / methanol / 2 h / 20 °C
3: pyridine / 16 h / 140 °C
4: hydrogenchloride / lithium hydroxide monohydrate; methanol / 2 h / 100 °C
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