反应详情

To a stirred solution of 2-chloro-5-(methylthio)benzoic acid (5 g, 24.67 mmol) in t-butanol (20 mL) was added triethylamine (5.25 mL, 37.8 mmol). After stirring briefly, diphenylphosphoryl azide (6 mL, 27.60 mmol) was added drop wise. The reaction mixture was slowly heated to reflux for 6 hours and then cooled to room temperature. The solvent was removed under reduced pressure and the crude reaction mixture was dissolved in tetrahydrofuran (12.5 mL) followed by the addition of 12.5 mL trifluoroacetic acid (1:1). The reaction mixture was heated to reflux for 6 hours and the solvent was evaporated after cooling to room temperature. The reaction mixture was treated with NaOH (25%) to bring the pH to 12 while cooling in an ice water bath. The product was repeatedly extracted into ethylacetate (4×25 mL) and the organic layer washed with water (10 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo to afford yellow oil. The product was purified by column chromatography (SiO2, gradient of hexanes/EtOAc) and the collected samples dissolved in ether and treated with HCl/ether (10 mL, 1M) to provide white crystals. The title product was a white solid (3.73 g, 87% yield): mp: 180-181° C.; TLC: hexanes/EtOAc (9:1) Rf=0.51; MS (Cl) m/e 174 (M+1 for C7H8ClNS) and m/e 191 (M+NH3), 1H-NMR (CDCl3) δ (ppm) 7.2-6.7 (m, 3H, Ar—H), 2.5 (s, 3H, S—CH3).

1. temperatureThe reaction mixture was slowly heated
2. temperatureto reflux for 6 hours
3. customThe solvent was removed under reduced pressure
4. customthe crude reaction mixture
5. temperatureThe reaction mixture was heated
6. temperatureto reflux for 6 hours
7. customthe solvent was evaporated
8. temperatureafter cooling to room temperature
9. additionThe reaction mixture was treated with NaOH (25%)
10. temperaturewhile cooling in an ice water bath
11. extractionThe product was repeatedly extracted into ethylacetate (4×25 mL)
12. washthe organic layer washed with water (10 mL)
13. dry with materialThe combined extracts were dried over MgSO4
14. concentrationconcentrated in vacuo
15. customto afford yellow oil
16. customThe product was purified by column chromatography (SiO2, gradient of hexanes/EtOAc)
17. dissolutionthe collected samples dissolved in ether
18. additiontreated with HCl/ether (10 mL, 1M)
19. customto provide white crystals