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CAS No. : | 42521-10-8 | MDL No. : | MFCD00173929 |
Formula : | C8H8ClNO3 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | DAPAXVAUEVRBGS-UHFFFAOYSA-N |
M.W : | 201.61 | Pubchem ID : | 13339618 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With potassium carbonate; In N,N-dimethyl-formamide; | Example 16.1; 2-Chloro-6-methoxy-isonicotinic acid methyl ester; To <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (16 g, 85.3 mmol) in DMF (220 mL) were added K2CO3 (47 g, 341 mmol) and Mel (6.37 mL, 102.3 mmol). After stirring overnight, the reaction mixture was filtered and then concentrated. The residue was dissolved in ethyl acetate, washed with water (3 times) and brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by flash column chromatography eluted with 10-30% ethyl acetate in hexanes gave the title product (15 g, 87%).1H NMR (300 MHz, CDCl3): delta 7.45 (s, 1H), 7.23 (s, 1H), 3.98 (s, 3H), 3.95 (s, 3H). |
87% | With potassium carbonate; In N,N-dimethyl-formamide; | Example 12.1; 2-Chloro-6-methoxy-isonicotinic acid methyl ester; To <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (16 g, 85 mmol) in DMF (220 mL) were added K2CO3 (47 g, 341 mmol) and MeI (6.37 mL, 102 mmol). After stirring for overnight, the reaction mixture was filtered and then concentrated. The residue was dissolved in ethyl acetate, washed with water (3 times) and brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by flash column chromatography eluted with 10-30% ethyl acetate in hexanes gave the title product (15 g, 87%).1H NMR (300 MHz, CDCl3): delta (ppm) 7.45 (s, 1H), 7.23 (s, 1H), 3.98 (s, 3H), 3.95 (s, 3H). |
87% | With potassium carbonate; In N,N-dimethyl-formamide; | Example 9.1; 2-Chloro-6-methoxy-isonicotinic acid methyl ester; To <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (16 g, 85.3 mmol) in DMF (220 mL) were added K2CO3 (47 g, 341.2 mmol) and MeI (6.37 mL, 102.3 mmol). After stirring for overnight, the reaction mixture was filtered and then concentrated. The residue was dissolved in ethyl acetate, washed with water (3 times) and brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by flash column chromatography eluted with 10-30% ethyl acetate in hexanes gave the title product (15 g, 87%).1H NMR (300 MHz, CDCl3): delta (ppm) 7.45 (s, 1H), 7.23 (s, 1H), 3.98 (s, 3H), 3.95 (s, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 65℃; for 20h; | a) To a suspension of <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (2.00 g, 10.7 mmol) in MeOH (100 mL), H2SO4 (2 mL) is added. The mixture is stirred at 65C for 20 h. The solution is cooled to rt. A precipitate forms. The solid material is collected, washed with MeOH and dried to give <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> methyl ester (1.66 g) as a white solid; LC- MS: tR = 1.29 min; [M+1]+ = 202.00. | |
With sulfuric acid; at 65℃; for 20h; | To a suspension of <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (2.00 g, 10.7 mmol) in methanol (100 mL), H2SO4 (2 mL) is added. The mixture is stirred at 65C for 20 h. The solution is cooled to rt. A precipitate forms. The solid material is collected, <n="49"/>washed with methanol and dried to give <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> methyl ester (1.66 g) as a white solid; LC-MS: tR = 1.29 min; [IVM]+ = 202.00. | |
With sulfuric acid; at 65℃; for 20h; | To a suspension of <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (2.00 g, 10.7 mmol) in MeOH (100 mL), H2SO4 (2 mL) is added. The mixture is stirred at 65 C. for 20 h. The solution is cooled to rt. A precipitate forms. The solid material is collected, washed with MeOH and dried to give <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> methyl ester (1.66 g) as a white solid; LC-MS: tR=1.29 min; [M+1]+=202.00. |
sulfuric acid; for 24h;Reflux; | b) To a suspension of <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (244 g, 1.30 mol) in methanol (2.5 L), H2SO4 (20 mL) is added. The mixture is stirred at reflux for 24 h before it is cooled to 0C. The solid material is collected, washed with methanol (200 mL) and water (500 mL) and dried under HV to give <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> methyl ester (165 g) as a white solid; LC-MS: tR = 0.94 min, [M+1]+ = 201.89. | |
With sulfuric acid; at 65℃; for 20h; | a) To a suspension of <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (2.00 g, 10.7 mmol) in methanol (100 mL), H2SO4 (2 mL) is added. The mixture is stirred at 65 C. for 20 h. The solution is cooled to rt. A precipitate forms. The solid material is collected, washed with methanol and dried to give <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> methyl ester (1.66 g) as a white solid; LC-MS: tR=1.29 min; [M+1]+=202.00. | |
With sulfuric acid; at 0℃; for 24h;Reflux; | b) To a suspension of <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (244 g, 1.30 mol) in methanol (2.5 L), H2SO4 (20 mL) is added. The mixture is stirred at reflux for 24 h before it is cooled to 0 C. The solid material is collected, washed with methanol (200 mL) and water (500 mL) and dried under HV to give <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> methyl ester (165 g) as a white solid; LC-MS: tR=0.94 min, [M+1]+=201.89. | |
165 g | With sulfuric acid; for 24h;Reflux; | b) To a suspension of <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (244 g, 1.30 mol) in methanol (2.5 L), H2SO4 (20 mL) is added. The mixture is stirred at reflux for 24 h before it is cooled to 0 C. The solid material is collected, washed with methanol (200 mL) and water (500 mL) and dried under HV to give <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> methyl ester (165 g) as a white solid; LC-MS: tR=0.94 min, [M+1]+=201.89. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With lithium borohydride; ethanol; In tetrahydrofuran; at 20℃; for 15h; | Step 2 To 33 (4.03 g, 20 mmol) in THF (50 mL) in a water bath was added LiBH4 (1.31 g, 60 mmol). Ethanol ( 10 mL) was added to the reaction mixture dropwise and the reaction mixture was stirred at room temperature for 15 h. Excess aqueous IN NaOH was added and the mixture was extracted with EtOAc. The combined organics were washed with water and brine, dried (MgS04), filtered, and concentrated in vacuo to provide 34 (3.43 g, 99%). |
In tetrahydrofuran; water; | (2-Chloro-6-methoxypyridin-4-yl)methanol To a solution of methyl (2-chloro-6-methoxypyridin-4-yl)carboxylate (15-1, 2.0 g, 9.92 mmole) in dry THF (40 mL) was added LiBH4 (7.4 mL, 2 M in THF, 14.88 mmole) then the mixture was heated to reflux. After 18 hr the mixture was cooled to RT and quenched by slow addition of H2O. The layers were separated and the aqueous layer extracted with EtOAc (2*). The combined organic layers were dried (MgSO4), filtered, and concentrated to give the titled compound a white solid which was sufficiently pure for use in the next step. 1H-NMR (500 MHz, CDCl3) delta 6.90 (s, 1 H), 6.65 (s, 1 H), 4.67 (m, 2 H), 3.94 (s, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; In methanol; for 24h;Reflux; | b) To a suspension of <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> (244 g, 1.30 mol) in methanol (2.5 L), H2S04 (20 mL) is added. The mixture is stirred at reflux for 24 h before it is cooled to 0C. The solid material is collected, washed with methanol (200 mL) and water (500 mL) and dried under HV to give <strong>[15855-06-8]2-chloro-6-methoxy-isonicotinic acid</strong> methyl ester (165 g) as a white solid; LC-MS: tR = 0.94 min, [M+1]+ = 201 .89. |
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