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), thionyl chloride (8 mL) was added slowly dropwise, and the reaction was stirred for 10 hours at room temperature. After completion of the reaction, the mixture was concentrated under reduced pressure 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 = 8.5 Hz, 2H), 7.29 (d, J = 8.6 Hz, 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 glyoxylate (1.27 g, 13.8 mmol) and copper(II) sulfate pentahydrate (0.35 g, 1.40 mmol) in a 2.5 M pyridine buffer and a 0.5 M acetic acid in aqueous solution and stirred for 10 h at room temperature. The reaction solution was extracted with dichloromethane (3 × 10 mL), the organic layers were combined, washed with 0.5 M HCl (3 × 20 mL), dried, filtered and concentrated under reduced pressure. The residue was purified by fast column chromatography (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 = 8.8 Hz, 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
[3] Angewandte Chemie - International Edition, 1997, vol. 37, # 19, p. 2708 - 2714
[4] Organic Letters, 2015, vol. 17, # 4, p. 1018 - 1021
[5] Journal of the American Chemical Society, 1978, vol. 100, p. 4555 - 4568
