4-Hydroxyphenyloxoacetic acid methyl ester

4-Hydroxyphenyloxoacetic acid methyl ester Property

storage temp. 

Inert atmosphere,Room Temperature

Appearance

White to off-white Solid

EPA Substance Registry System

Benzeneacetic acid, 4-hydroxy-.alpha.-oxo-, methyl ester (38250-16-7)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

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

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

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.

4-Hydroxyphenyloxoacetic acid methyl ester Chemical Properties,Usage,Production

Synthesis

Step 1: (R)-2-Amino-2-(4-hydroxyphenyl)acetic acid (D-4-hydroxyphenylglycine, 10.0 g, 60.1 mmol) was dissolved in methanol (200 mL) and thionyl chloride (8 mL) was added slowly and dropwise. The reaction mixture was stirred at room temperature for 10 hours. After completion of the reaction, the solvent was removed by vacuum concentration and the residue was washed twice with ether to afford methyl (R)-2-amino-2-(4-hydroxyphenyl)acetate (D-4-hydroxyphenylglycine methyl ester, 13.0 g, 60.0 mmol, 100% yield) as a white solid.1H NMR (300 MHz, DMSO-d6) δ 3.68 (s, 3H) 5.07 (s, 1H), 6.85 (d, J=8.5Hz, 2H), 7.29 (d, J=8.6Hz, 2H), 9.03 (s, 3H), 10.02 (s, 1H). Step 2: Methyl (R)-2-amino-2-(4-hydroxyphenyl)acetate (D-4-hydroxyphenylglycine methyl ester, 0.302 g, 1.39 mmol) was dissolved in freshly prepared glyoxalic acid (1.27 g, 13.8 mmol) and copper(II) sulfate pentahydrate (0.35 g, 1.40 mmol) in 2.5 M pyridine buffer and 0.5 M acetic acid in an aqueous solution. The reaction mixture was stirred at room temperature for 10 hours. Upon completion of the reaction, it was extracted with dichloromethane (10 mL x 3), the organic layers were combined, washed with 0.5 M HCl (20 mL x 3), dried, filtered and concentrated in vacuum. The residue was purified by flash column (silica gel, chloroform elution) to afford methyl 2-(4-hydroxyphenyl)-2-oxoacetate (0.109 g, 6.06 mmol, 44% yield) as a clear oil.1H NMR (300 MHz, CDCl3) δ 3.99 (s, 3H), 5.41 (br s, 1H), 6.95 (d, J=8.8 Hz, 2H), 8.00 (d, J=8.8Hz, 2H).

References

[1] Journal of Medicinal Chemistry, 2002, vol. 45, # 18, p. 3946 - 3952
[2] Patent: WO2013/33093, 2013, A1. Location in patent: Page/Page column 137; 138