Triethylamine → 2-(2-Methylcyclopropyl)benzoxazole-4-carboxylic acid

To an ice-cold solution of 2-methylcyclopropanecarboxylic acid (214 mg, 2.14 mmol) in dichloromethane (10 mL) was added oxalyl chloride (0.19 mL, 2.14 mmol) dropwise and a few drops of DMF. The ice bath was removed and stirring was continued for 1 h. 2-Amino-3-hydroxybenzoic acid hydrobromide (500 mg, 2.14 mmol) was added followed by triethylamine (0.90 mL, 6.42 mmol). The resulting reaction mixture was stirred at room temperature overnight. The reaction was quenched with aqueous 1 N HCl (25 mL) until the solution reached pH 1. The reaction mixture was extracted with dichloromethane. The combined organic layers were dried over Na2SO4, filtered and concentrated to a brown solid. The crude was dissolved in toluene (10 mL) and the solution was treated with p-toluenesulfonic acid monohydrate (574 mg, 3.0 mmol). The reaction mixture was then heated to reflux for 5 h. The reaction was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was separated then washed with water (5×150 mL), brine, dried (Na2SO4), filtered and concentrated to afford 2-(2-methylcyclopropyl)benzoxazole-4-carboxylic acid (409 mg, 88%) as a yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 12.92 (br s, 1H), 7.84 (dd, J=8.1, 1.0 Hz, 1H), 7.81 (dd, J=7.8, 1.0 Hz, 1H), 7.38 (t, J=7.9 Hz, 1H), 2.10-2.05 (m, 1H), 1.62-1.57 (m, 1H), 1.41-1.34 (m, 1H), 1.28 (d, J=6.5 Hz, 3H), 1.08-1.02 (m, 1H); MS (ESI+) m/z 218 (M+H).

1. customThe ice bath was removed
2. customThe resulting reaction mixture
3. stirringwas stirred at room temperature overnight
4. customThe reaction was quenched with aqueous 1 N HCl (25 mL) until the solution
5. extractionThe reaction mixture was extracted with dichloromethane
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated to a brown solid
9. dissolutionThe crude was dissolved in toluene (10 mL)
10. temperatureThe reaction mixture was then heated
11. temperatureto reflux for 5 h
12. extractionextracted with ethyl acetate
13. customThe organic layer was separated
14. washthen washed with water (5×150 mL), brine
15. dry with materialdried (Na2SO4)
16. filtrationfiltered
17. concentrationconcentrated

ORDレコード

ord-6094fd35946e4d1593b92f2423050307

出典データセット

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07553846B2