2-AMINO-5-CHLORO-NICOTINIC ACID METHYL ESTER Chemical Properties

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

Appearance

Light yellow to brown Solid

InChI

InChI=1S/C7H7ClN2O2/c1-12-7(11)5-2-4(8)3-10-6(5)9/h2-3H,1H3,(H2,9,10)

InChIKey

PEYKGXOKTQNWCI-UHFFFAOYSA-N

SMILES

C1(N)=NC=C(Cl)C=C1C(OC)=O

Safety Information

HS Code 

2933399990

2-AMINO-5-CHLORO-NICOTINIC ACID METHYL ESTER Usage And Synthesis

Synthesis

The general procedure for the synthesis of 2-amino-5-chloronicotinic acid methyl ester from 2,5-dichloronicotinic acid was as follows: first, 2,5-dichloronicotinic acid (20.2 g, 0.105 mol) was dissolved in methanol (500 mL) and cooled to 0 °C. Subsequently, pure thionyl chloride (38 mL, 63 g, 0.525 mol) was slowly added and the reaction temperature was kept at 0 °C with stirring for 1 hour. After that, the cooling bath was removed and the reaction mixture was allowed to warm up to room temperature and stirring was continued for 2 days. After completion of the reaction, the solvent was removed by distillation under reduced pressure to give an off-white residue. The residue was dissolved in ether (~500 mL) and washed sequentially with saturated aqueous NaHCO3 solution (~300 mL), water (~300 mL) and brine (~300 mL). The organic layer was separated, dried with anhydrous MgSO4 and filtered. The solvent was again removed by distillation under reduced pressure to afford methyl 2,5-dichloronicotinate (21.0 g, 97% yield) as a white solid. Next, the reaction was carried out in parallel in two pressure vessels by dissolving methyl 2,5-dichloronicotinate (4.5 g, 22 mmol) in an ammonia solution (250 mL, 0.5 M; 0.125 mol) in 1,4-dioxane. The pressure vessel was sealed and heated at 85±5°C for 9 days. After completion of the reaction, it was cooled to room temperature, the reaction mixture was combined and concentrated under reduced pressure to give a white solid. The solid was dissolved in a 1:1 acetone-methanol solvent mixture (about 500 mL), adsorbed onto silica gel (25 g) and purified by fast column chromatography (25:10:1 hexane-dichloromethane-ether solvent mixture) to afford methyl 2-amino-5-chloronicotinate (6.08 g, 75% yield). Finally, a solution of LiOH-H2O (1.38 g, 33 mmol) in water (33 mL) was added at once to a methanol (110 mL) suspension of methyl 2-amino-5-chloronicotinate (6.08 g, 27 mmol). The reaction mixture was stirred at 70 °C for 24 h. The reaction mixture gradually became homogeneous. After removing the solvent under reduced pressure, the resulting white solid was dried under vacuum (<1 mmHg) to constant weight to afford lithium 2-amino-5-chloronicotinate (5.51 g, 95% yield).

References

[1] Patent: WO2006/88840, 2006, A1. Location in patent: Page/Page column 126-127
[2] Patent: WO2006/91428, 2006, A2. Location in patent: Page/Page column 124
[3] Patent: WO2006/88837, 2006, A2. Location in patent: Page/Page column 120
[4] Patent: WO2007/109238, 2007, A1. Location in patent: Page/Page column 99-100

2-AMINO-5-CHLORO-NICOTINIC ACID METHYL ESTER(50735-33-6)Related Product Information

• 5-Amino-2-chloro-nicotinic acid methyl ester
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• 2-AMINO-5-CHLORO-3-PICOLINE
• 2-amino-5-chloronicotinaldehyde
• 2-AMINO-5-CHLORO-NICOTINIC ACID METHYL ESTER