Triethylamine → 2-Cyclopentylbenzoxazole-4-carboxylic acid

To a suspension of 2-amino-3-hydroxybenzoic acid hydrobromide (300 mg, 1.28 mmol) in dichloromethane (8 mL) was added cyclopentane carbonyl chloride (0.16 mL, 1.28 mmol). The resulting reaction mixture was stirred at room temperature for 10 min, then triethylamine (0.71 mL, 5.13 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction was diluted in dichloromethane (30 mL) and quenched with aqueous 2 N HCl (10 mL) until the solution reached pH 1. The aqueous layer was further extracted with dichloromethane (2×30 mL). The organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated to an orange solid. The amide product was directly re-dissolved in toluene (8 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (296 mg, 1.56 mmol). The reaction mixture was then heated to reflux for 3 h. The reaction was cooled to room temperature and the toluene was evaporated. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was separated, washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel, 9:1 to 3:1 ethyl acetate/methanol) to afford 2-cyclopentylbenzoxazole-4-carboxylic acid (179 mg, 75%) as a pale orange solid: 1H NMR (500 MHz, DMSO-d6) δ 7.85-7.72 (m, 2H), 7.39-7.29 (m, 1H), 2.05-1.50 (m, 9H); MS (ESI+) m/z 232 (M+H).

1. customThe resulting reaction mixture
2. stirringthe reaction mixture was stirred at room temperature overnight
3. customquenched with aqueous 2 N HCl (10 mL) until the solution
4. extractionThe aqueous layer was further extracted with dichloromethane (2×30 mL)
5. washThe organic layers were washed with water and brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated to an orange solid
9. dissolutionThe amide product was directly re-dissolved in toluene (8 mL)
10. temperatureThe reaction mixture was then heated
11. temperatureto reflux for 3 h
12. temperatureThe reaction was cooled to room temperature
13. customthe toluene was evaporated
14. additionThe reaction mixture was poured into water
15. extractionextracted with ethyl acetate
16. customThe organic layer was separated
17. washwashed with water, brine
18. dry with materialdried over Na2SO4
19. filtrationfiltered
20. concentrationconcentrated
21. customThe crude product was purified by column chromatography (silica gel, 9:1 to 3:1 ethyl acetate/methanol)

ORD 기록

ord-557fe9b7d2dd4bb9968d9e5de6744efc

출처 데이터셋

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07553846B2