Benzoic acid, 3-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methoxy- (9CI)

Benzoic acid, 3-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methoxy- (9CI) Property

Boiling point:

364.8±32.0 °C(Predicted)

Density 

1.243±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

pka

4.42±0.10(Predicted)

Appearance

Off-white to light brown Solid

Safety

HS Code 

29225090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

Benzoic acid, 3-[[(1,1-dimethylethoxy)carbonyl]amino]-4-methoxy- (9CI) Chemical Properties,Usage,Production

Chemical Properties

White powder

Synthesis

General procedure for the synthesis of Boc-3-amino-4-methoxybenzoic acid from di-tert-butyl dicarbonate and 3-amino-4-methoxybenzoic acid: 3-amino-4-methoxybenzoic acid (20.0 g, 119 mmol) was suspended in a solvent mixture of 1 mol/L aqueous NaOH (180 mL) and THF (150 mL). The reaction mixture was cooled in an ice bath. A solution of di-tert-butyl dicarbonate (104.4 g, 479 mmol) in THF (70 mL) was slowly added dropwise under stirring conditions for 30 min. After completion of the dropwise addition, the ice bath was removed and the reaction mixture was continued to be stirred at room temperature for 12 hours. Upon completion of the reaction, THF was removed by distillation under reduced pressure.The remaining aqueous phase was diluted with distilled water and subsequently extracted three times with ethyl acetate (3 × 70 mL). The aqueous phase was acidified to pH 4-5 with concentrated hydrochloric acid and extracted with ethyl acetate (3 × 80 mL). All organic phases were combined, washed with distilled water, and dried over anhydrous sodium sulfate. After filtration, Boc-3-amino-4-methoxybenzoic acid (20.78 g, 65% yield) was obtained as an off-white solid by concentration under reduced pressure, which could be used in the next reaction without further purification.

References

[1] European Journal of Organic Chemistry, 2001, # 2, p. 311 - 322
[2] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 80 - 90
[3] Patent: CN104817489, 2017, B. Location in patent: Paragraph 0037-0040
[4] Patent: US2011/178108, 2011, A1. Location in patent: Page/Page column 17