2-Chloro-4-(Methoxycarbonyl)benzoic acid

2-Chloro-4-(Methoxycarbonyl)benzoic acid Property

Boiling point:

360.3±27.0 °C(Predicted)

Density 

1.413±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

2.43±0.25(Predicted)

Appearance

Off-white to light brown Solid

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

2-Chloro-4-(Methoxycarbonyl)benzoic acid Chemical Properties,Usage,Production

Synthesis

General procedure for the synthesis of 2-chloro-4-(methoxycarbonyl)benzoic acid from dimethyl 2-chloroterephthalate: dimethyl 2-chloroterephthalate (2.5 g, 11 mmol) was dissolved in dichloromethane (20 mL) and cooled to -5 °C. Boron tribromide (1 M in dichloromethane, 11 mL, 11 mmol) was slowly added dropwise with stirring. After the dropwise addition was completed, the reaction mixture was gradually warmed to room temperature and stirring was continued for 18 hours. Upon completion of the reaction, the mixture was poured into ice water, allowed to warm to room temperature, and then the pH was adjusted with solid sodium bicarbonate to 8. The aqueous phase was washed with ethyl acetate (50 mL), followed by acidification with 1 M hydrochloric acid, and extraction with ethyl acetate (160 mL). The organic phases were combined, washed with brine (80 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (120 g of silica gel, eluent was a 0-10% solution of methanol (containing 5% acetic acid) in dichloromethane) to give 2-chloro-4-(methoxycarbonyl)benzoic acid (1.5 g, 62% yield) as a white solid. Mass spectrum (electrospray positive ion mode) m/z 215 [M+H]+, (electrospray negative ion mode) m/z 213 [M-H]-; NMR hydrogen spectrum (400 MHz, DMSO-d6) δ: 13.79 (1H, broad single peak), 8.00-7.95 (2H, multiple peaks), 7.90-7.88 (1H, multiple peaks), 3.89 (3H (single peak).

References

[1] Patent: WO2016/97004, 2016, A1. Location in patent: Page/Page column 112
[2] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 22, p. 6748 - 6753
[3] Patent: WO2009/126863, 2009, A2. Location in patent: Page/Page column 119-120
[4] Patent: US2006/63779, 2006, A1. Location in patent: Page/Page column 88-89