反应详情

To a solution of 6-chloro-5-(4-hydroxymethyl-phenyl)-1H-indole-3-carbaldehyde (422 mg, 1.48 mmol) in MeCN (18 mL), tert-butanol (18 mL) and 2-methyl-2-butene (12 mL, 110 mmol) at 0° C. was added a solution of sodium chlorite (1.25 g, 14.8 mmol) and sodium phosphate monobasic hydrate (2.04 g, 14.8 mmol) in water (9 mL) dropwise. The ice bath was removed and the solution was stirred at room temperature. After 5 hours, additional 2-methyl-2-butene (3 mL, 27.5 mmol) was added, followed by sodium chlorite (1.25 g, 14.8 mmol) and sodium phosphate monobasic hydrate (2.04 g, 14.8 mmol) in water (9 mL) dropwise. The resulting solution was stirred at room temperature. After 27 hours total reaction time, the solution was concentrated in vacuo to afford a pale yellow solid. Water (5 mL) was added to the solid and the mixture was extracted with EtOAc (2×50 mL). The combined organic layers were concentrated in vacuo and purified by flash chromatography (35-90% EtOAc/heptane, with 0.2% formic acid modifier) to afford a pale yellow solid. The solid was stirred in EtOAc (5 mL) at 55° C. for 6 hours, and the resulting slurry was cooled to room temperature. The precipitate was filtered and washed with EtOAc (1 mL) to afford the title compound (182 mg, 41% yield) as a cream-colored crystalline solid. MS (ES+) 300.0 (M−H)+. 1H NMR (400 MHz, CD3OD) δ 8.00 (s, 1 H) 7.98 (s, 1 H) 7.56 (s, 1 H) 7.40 (m, 4 H) 4.65 (s, 2 H).

1. customThe ice bath was removed
2. stirringThe resulting solution was stirred at room temperature
3. waitAfter 27 hours total reaction time
4. concentrationthe solution was concentrated in vacuo
5. customto afford a pale yellow solid
6. extractionthe mixture was extracted with EtOAc (2×50 mL)
7. concentrationThe combined organic layers were concentrated in vacuo
8. custompurified by flash chromatography (35-90% EtOAc/heptane, with 0.2% formic acid modifier)
9. customto afford a pale yellow solid
10. temperaturethe resulting slurry was cooled to room temperature
11. filtrationThe precipitate was filtered
12. washwashed with EtOAc (1 mL)