4-HYDROXY-3-METHOXY-5-NITROBENZOIC ACID Chemical Properties

Melting point:

216℃

Boiling point:

386℃

Density 

1.564

Flash point:

187℃

storage temp. 

Sealed in dry,Room Temperature

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

3.82±0.10(Predicted)

color 

Pale Yellow to Yellow

InChI

InChI=1S/C8H7NO6/c1-15-6-3-4(8(11)12)2-5(7(6)10)9(13)14/h2-3,10H,1H3,(H,11,12)

InChIKey

AEDVAGWYAKIOIM-UHFFFAOYSA-N

SMILES

C(O)(=O)C1=CC([N+]([O-])=O)=C(O)C(OC)=C1

4-HYDROXY-3-METHOXY-5-NITROBENZOIC ACID Usage And Synthesis

Uses

4-Hydroxy-3-methoxy-5-nitrobenzoic acid is used as an intermediate for Opicapone. Opicapone is a catechol-O-methyltransferase (COMT) inhibitor used to increase the availability and duration of action of L-Dopa, the standard of care for Parkinson's disease.

Synthesis

The general procedure for the synthesis of 4-hydroxy-3-methoxy-5-nitrobenzoic acid from vanillic acid was as follows: vanillic acid (20 g, 119 mmol) was dissolved in acetic acid (200 mL) and 60% nitric acid (9.7 mL, 126.4 mmol) was added slowly and dropwise. The reaction mixture was stirred at room temperature for 30 min and then poured into ice water to quench the reaction. The precipitate precipitated was collected by filtration, washed well with water and dried under vacuum to afford the target product 4-hydroxy-3-methoxy-5-nitrobenzoic acid as a yellow powder. The yield was 11.28 g (44% yield) and the melting point range was 216-219 °C (literature value 216 °C).

References

[1] Journal of Medicinal Chemistry, 2010, vol. 53, # 8, p. 3396 - 3411
[2] Chemistry Letters, 2016, vol. 45, # 4, p. 439 - 441
[3] Patent: EP1845097, 2007, A1. Location in patent: Page/Page column 7
[4] Patent: WO2013/89573, 2013, A1. Location in patent: Page/Page column 17-18