Ethyl 3-hydroxybenzeneacetate

Light Yellow Liquid

Intermediate 5; (2-Cyclopropyl-5-hydroxy-phenyl)-acetic acid ethyl ester; [0089] Step A; (3-Hydroxy-phenyl)-acetic acid (10 g, 65.7 mmol) is dissolved inEtOH (50 mL). Catalytic amounts of thionyl chloride (~0.5 mL) are added and the solution is stirred for 6 h at rt. The solvent is removed in vacuo to give (3-hydroxy-phenyl)-acetic acid ethyl ester 1 (11.8 g, quant.): MS calcd. for CiIntermediate 10; (2-Cyclopropyl-5-hydroxy-phenyl)-acetic acid ethyl ester; Step A; (3-Hydroxy-phenyl)-acetic acid (10 g, 65.7 mmol) is dissolved in EtOH (60 mL). Catalytic amounts of thionyl chloride (~0.5 mL) are added and the solution is stirred for 6 h at rt. The solvent is removed in vacuo to give (3-hydroxy-phenyl)-acetic acid ethyl ester 6 (11.8 g, quant): MS calcd. for CEthyl 2-(3-hydroxyphenyI)acetate (S16-2).; To a solution of 2-(3-hydroxyphenyl)acetic acid (S16-1; 10 g, 65.8 mmol) in 200 mL of ethanol was added 8 mL of concentrated sulfuric acid. The resulting mixture was refluxed overnight and condensed under vacuum. The residue was dissolved in ethyl acetate and washed with water. The organic layer was combined, washed with brine, dried over MgS0Ethanol (616.7 mL), 12 (100.0 g, 657.9 mmol) and concentratedsulfuric acid (15.3 g, 131.6 mmol) were mixed by stirring and heatedto reflux for 2 h. The resulting mixture was cooled to ambienttemperature and evaporated under vacuum to remove the ethanol. Theresidue was then extracted with dichloromethane (50 mL × 3). Thecombined organic layer was washed with water until neutral, dried overwith anhydrous magnesium sulphate, and filtered and concentratedunder vacuum to give a pale-brown liquid (115.6 g, based on 12 yield of98percent, purity of 99percent, area normalisation method of HPLC). 1H NMR:(CDCl3, 500 MHz, δ: ppm), 7.19–7.16 (t, 1H, J = 7.5 Hz), 6.83–6.82 (d, 1H, J = 8.0 Hz), 6.77 (s, 1H), 6.74–6.72 (q, 1H, J = 2.0 Hz), 5.55 (s, 1H), 4.18–4.14 (q, 2H, J = 7.5 Hz), 3.56 (s, 2H), 1.27–1.24 (t, 3H, J = 7.0 Hz).1H NMR data corresponded to the literature.29Example B.5 Synthesis of 3-Hydroxyphenylacetic acid ethyl ester: Concentrated Ha) Thionylchloride (17.5 mL, 240 mmol) was added dropwise to ethanol (200 mL) at 0C, andthe mixture was stirred for 15 min. To the solution was added 3-hydroxyphenylaceticacid (24.3 g, 160 mmol), and the mixture was stirred at room temperature for 20h. The solvent was removed under reduced pressure and the residue was dissolvedin diethyl ether (200 mL). To the solution was added calcium carbonate (16.0 g)and the mixture was stirred for 30 min. The insoluble materials were filteredoff and the filtrate was concentrated under reduced pressure. The residue wastriturated with hexane to give the title compound (26.3 g, 91percent) as a colorless solid.A.

A useful synthetic intermediate for the preparation of novel antiinflammatory agents.

Molecular Weight:180.20
XLogP3:1.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:180.078644241
Monoisotopic Mass:180.078644241
Topological Polar Surface Area:46.5
Heavy Atom Count:13
Complexity:168
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes