Triethylamine → HCID 68996723, compound

A mixture of 1-(tert-butoxycarbonyl)piperidin-4-carboxylic acid (2.47 g, 10.78 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.43 g, 17.96 mmol), 1-hydroxybenzotriazole (2.42 g, 17.96 mmol) and methyl 2-amino-3-hydroxybenzoate (1.50 g, 8.98 mmol) in dichloromethane (25 mL) was stirred under nitrogen at room temperature for 10 min, and then triethylamine (1.47 mL, 10.6 mmol) was added. The resulting reaction mixture was stirred at room temperature for 5 h, the reaction was quenched with a saturated aqueous solution of sodium bicarbonate (15 mL), and then extracted with dichloromethane (2×150 mL). The combined organic phase was washed with water (2×100 mL), brine (2×100 mL), and dried (Na2SO4), filtered and concentrated to afford a light yellow solid. The crude solid was dissolved in toluene (20 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (2.08 g, 10.9 mmol). The reaction mixture was then heated to reflux under nitrogen for 4 h. The reaction was cooled to room temperature and concentrated. The crude product was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford 2-(piperidin-4-yl)benzoxazole-4-carboxylate methyl ester (1.64 mg, 70%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 7.99 (dd, J=7.8, 0.9 Hz, 1H), 7.78 (dd, J=7.8, 0.9 Hz, 1H), 7.39 (t, J=7.8 Hz, 1H), 4.00 (s, 3H), 3.52-3.45 (m, 2H), 3.36-3.30 (m, 1H), 3.10-3.03 (m, 2H), 2.33-2.20 (m, 4H); MS (ESI+) m/z 261 (M+H).

1. customThe resulting reaction mixture
2. stirringwas stirred at room temperature for 5 h
3. customthe reaction was quenched with a saturated aqueous solution of sodium bicarbonate (15 mL)
4. extractionextracted with dichloromethane (2×150 mL)
5. washThe combined organic phase was washed with water (2×100 mL), brine (2×100 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a light yellow solid
10. temperatureThe reaction mixture was then heated
11. temperatureto reflux under nitrogen for 4 h
12. temperatureThe reaction was cooled to room temperature
13. concentrationconcentrated
14. customThe crude product was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide)

ORD record

ord-079714eda3a24b2194ff3305a57e210b

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07553846B2