Methyl 3-hydroxy-4-methoxybenzoate

Methyl 3-hydroxy-4-methoxybenzoate Property

Melting point:

64-67 °C (lit.)

Boiling point:

102 °C(Press: 0.1 Torr)

Density 

1.216±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

form 

powder to crystal

pka

9.15±0.10(Predicted)

color 

Light yellow to Brown

InChI

InChI=1S/C9H10O4/c1-12-8-4-3-6(5-7(8)10)9(11)13-2/h3-5,10H,1-2H3

InChIKey

QXOXUEFXRSIYSW-UHFFFAOYSA-N

SMILES

C(OC)(=O)C1=CC=C(OC)C(O)=C1

LogP

1.750 (est)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29189990

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

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

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

Methyl 3-hydroxy-4-methoxybenzoate Chemical Properties,Usage,Production

Chemical Properties

Off-white to beige crystalline powder

Uses

Methyl 3-hydroxy-4-methoxybenzoate may be used as starting reagent in the novel synthesis of gefitinib. Synthesis involves the alkylation of starting material, followed by nitration, reduction, cyclization, chlorination and two successive amination reactions. It may be used as starting reagent in the synthesis of methyl 5-(benzo[d][1,3]dioxol-5-yl)-4-methoxy-2-nitrobenzoate.

Synthesis

To a dry 100 mL three-necked flask, 10 g of 3-hydroxy-4-methoxybenzoic acid, 110 mL of methanol, and 360 μL of concentrated sulfuric acid were sequentially added, and the mixture was heated to 65 °C and reacted under magnetic stirring overnight. The reaction process was monitored by thin layer chromatography (unfolding agent: ethyl acetate/dichloromethane=1:1). Upon completion of the reaction, the reaction mixture was transferred to a round bottom flask and methanol was removed by distillation under reduced pressure. The residue was extracted with 25 mL of ethyl acetate and neutralized with 15 mL of saturated sodium bicarbonate solution. After evaporation of ethyl acetate, the solid product methyl 3-hydroxy-4-methoxybenzoate was obtained as 9.06 g in 83.6% yield.

References

[1] Patent: WO2005/9389, 2005, A2. Location in patent: Page/Page column 139
[2] Patent: WO2005/9389, 2005, A2. Location in patent: Page/Page column 139
[3] Journal of Organic Chemistry, 1985, vol. 50, # 2, p. 217 - 231
[4] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 20, p. 2893 - 2897
[5] Organic and Biomolecular Chemistry, 2016, vol. 14, # 11, p. 3061 - 3068