反应详情

温度

0.6000000238418579 °C

(3-Bromo-pyridin-2-yl)-methanol (7.39 g, 39.30 mmoles), and triethylamine (7.15 mL, 51.3 mmoles) are combined in tetrahydrofuran (70 mL) under nitrogen. The solution is chilled to 0.6° C. with an ice bath. Methanesulfonyl chloride (3.35 mL, 43.28 mmol) is added dropwise over 20 min, controlling the exotherm such that the internal temperature does not exceed 5° C. Following the addition, the reaction is stirred over an ice bath. After 20 min HPLC analysis shows that the (3-Bromo-pyridin-2-yl)-methanol is fully consumed. Triethylamine hydrochloride is filtered using a fitted glass funnel, washing with cold THF (50 mL). The THF filtrate containing the mesylate is placed under nitrogen and chilled in an ice bath. 2-Iodo-5-chlorophenol (10.00 g, 39.30 mmoles) is added, followed by addition of sodium t-butoxide (4.10 g, 41.38 mmol) in two equal portions with a mild exotherm of about 5° C. for each addition. The ice bath is removed and the reaction allowed to stir overnight. The reaction is quenched with water (50 mL) and the lower aqueous layer allowed to slowly separate. The organic portion is washed with brine (25 mL), and then the brine and aqueous portions back-extracted with THF (10 mL). The organic portions are combined and dried over sodium sulfate, filtered, and concentrated to afford a rusty orange solid. The solid is dissolved in dichloromethane (25 mL) and chromatographed on an AnaLogix Inc., Intelliflash 180 automated chromatography instrument, version 1.8.0. using a gradient of 10- 20% ethyl acetate/hexanes over 35 min to afford 11.0 g (65%) of the product as a yellow solid. 1H NMR (DMSO) δ 5.31 (2H, s), 6.85 (1H, dd), 7.25 (1H, m), 7.39 (1H, dd), 7.77 (1H, d), 8.17 (1H, d), 8.59 (1H, d).

1. customdoes not exceed 5° C
2. additionthe addition
3. customis fully consumed
4. filtrationTriethylamine hydrochloride is filtered
5. washwashing with cold THF (50 mL)
6. additionThe THF filtrate containing the mesylate
7. temperaturechilled in an ice bath
8. customThe ice bath is removed
9. stirringto stir overnight
10. customThe reaction is quenched with water (50 mL)
11. customto slowly separate
12. washThe organic portion is washed with brine (25 mL)
13. extractionthe brine and aqueous portions back-extracted with THF (10 mL)
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. customto afford a rusty orange solid
18. customchromatographed on an AnaLogix Inc
19. customover 35 min