5-Methoxy-2-methylindole-3-acetic acid methyl ester

Brown Solid

General procedure: A reaction mixture containing the indoleacetic acid derivative (1 equivalent) and BOP-Cl (1 equivalent) in 3 mL/mmol of anhydrous CH2Cl2 is treated with triethylamine (2 equivalents) and aged at ambient temperature for 5 min. The mixture is combined with anhydrous methanol (0.14 mL/mmol) and then continuously stirred overnight at room temperature. Following dilution with dichloromethane (12 mL/mmol), the organic solution is washed with water (2x6 mL/mmol), dried over Na2SO4, and filtered. The organic filtrate is collected and concentrated in vacuo and the crude ester is purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to afford the title compound at first as viscous yellow oil, which stably crystallizes upon seeding and subsequent cold storage.General procedure: Indomethacin (3.00 g, 8.39 mmol) was dissolved in 1 M NaOH(200 mL) and left to stir overnight. The reaction was acidified with1 M HCl and the precipitate filtered off. Filtrate was then extractedthree times with DCM (100 mL). Combined organic layer was driedover Na2SO4 and concentrated in vacuo to give crude 2-(5-methoxy-2-methyl-1H-indol-3-yl)acetic acid (1.12 g, 5.15 mmol). Thecrude intermediate was dissolved in MeOH (50 mL) and TMSCl(1.86 mL, 14.73 mmol) was added. The reaction mixture was leftto stir at room temperature overnight. Water (50 mL) was addedto quench the reaction and extracted three times with DCM(50 mL). Organic layer was combined, dried over Na2SO4 and concentratedin vacuo. Residue obtained was purified by column chromatographyusing CHCl3:EtOAc (10:1) to give 12 as a brown solid(0.99 g, 83percent). 1H NMR (400 MHz, CDCl3) d 7.92 (s, 1H), 7.07 (d, J = 8.7 Hz, 1H), 7.01 (d, J = 2.0 Hz, 1H), 6.81–6.75 (m, 1H), 3.87 (d, J = 1.1 Hz, 3H), 3.68 (d, J = 1.0 Hz, 5H), 2.32 (s, 3H). 13C NMR(101 MHz, CDCl3) d 172.8, 154.1, 133.7, 130.2, 129.0, 111.1, 110.8, 104.1, 100.4, 55.9, 51.9, 30.3, 11.7.

Intermediate in the preparation of Indomethacin

Molecular Weight:233.26
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:233.10519334
Monoisotopic Mass:233.10519334
Topological Polar Surface Area:51.3
Heavy Atom Count:17
Complexity:282
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes