3-Pyridinecarboxylic acid, 2-chloro-, methyl ester

To the 250 ml flask is added in three 15.76g (0.1 µM) 2 - chloro -3 - picolinic acid, 100 ml methanol, under the ice-bath adds by drops 17.85g (0.15 µM) thionyl chloride, stirring and heating to reflux, the stirring reaction 8h. Thin layer chromatography tracking response, the raw materials point disappears, stopping the reaction. Reduced pressure distillation to remove the solvent to obtain light yellow 15.95g, yield 93percent(1)Example 136; Preparation of 2-chloro-pyridine-3-carboxylic acid methyl esterA mixture a 2-chloro nicotinic acid (2.0 g, 12.7 mmol), trimethyl ortho formate (8 ml) and methanol (10 drops) was heated to 15OIntermediate 3. 2-Chloronicotinic acid methyl ester.; To a room temperature solution of2-chloronicotinic acid (5.00 g, 31.7 mmol) in 20percent MeOH/toluene (100 mL) was added TMS diazomethane (trimethylsilyl diazomethane) (2.0M in hexanes, 31.7 mL) dropwise and the reaction was monitored by TLC (thin-layer chromatography) until completion. The reaction was concentrated down under reduced pressure. The residue was purified by silica chromatography using a gradient of hexanes:EtOAc (100:0) to hexanes:EtOAc (80:20) to yield 4.65 g (85.42percent) of Intermediate 3 as a yellow oil. EPO In a reactor, 59 mL (0.5 mol) of methyl cyanoacetate was added to the reactor, N-ethylpyridine tetrafluoroborate 50 mL, 3-dimethylaminopropenal 62 mL (0.5 mol) was homogeneously mixed, Microwave heating to 140 temperature and heat for 1h to carry out the reaction, TLC detection (oilEther: methylene chloride 1: 2 developed, sublimed iodine color)3-dimethylaminopropenal reaction completely, cooled to room temperature, organic solvent BEther 60mL extraction 3 times, residual phase ion water washing vacuum drying after repeated use, organic phase into the dry HCl gas, HPLC withThe reaction is continued until the reaction ends. Add the mass fraction of 20percent sodium hydroxide solution to adjust the pH = 5-6, separated, the water layer with ether20mL × 3 times extraction, combined organic layer, washed with water, molecular sieve drying, filtration, evaporation of solvent ether recovery, the residue byThe product was distilled at 110-115 ° C / 1 mmHg to prepare methyl 2-chloronicotinate and 80.6 g of colorless liquid in a yield of 93.9percent.In a 500 mL three-necked flask equipped with a thermometer, 69 mL (0.5 mol) of N, N-dibutylaminocrolein and K2CO3 5.0 g were added first, and then methyl cyanoacetate (65 mL (0.6 mol)) was added to prepare. A good device is placed in the sonicator. Ultrasonic radiation conditions were set, and the reaction was carried out at a temperature of 60°C, an ultrasonic power of 300 W, and a frequency of 100 KHz TLC test (petroleum ether:dichloromethane 1:2 development, sublimation iodine development) N, N-dibutylene Amine acrolein reaction is complete. After that, HCl gas was again introduced, the ultrasonic radiation was the same as above, and the reaction was for about 50 min. The reaction was followed by HPLC until the reaction was completed. After the reaction is completed, add sodium carbonate solution to adjust pΗ = 5-6, and separate the liquid. The aqueous layer is extracted with ethyl acetate 20 mL×3. The organic layers are combined, and the organic layer is washed with deionized water (10 mL). The organic layer is dried overnight and filtered. The solvent was evaporated by heating and the residue was distilled under reduced pressure. The 110-115 °C/lmmHg fraction was collected to obtain methyl 2-chloronicotinate, 79.5 g of a colorless liquid, and the yield was 92.7percent.

Molecular Weight:171.58
XLogP3:1.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:171.0087061
Monoisotopic Mass:171.0087061
Topological Polar Surface Area:39.2
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes