反应详情

温度

2.5 °C

[2-(4-Bromo-3-fluoro-phenyl)-2-hydroxy-ethyl]-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester (25.3 g, 66.9 mmol) and triuethylamine (10.2 g, 14.0 ml, 100 mmol) were combined with tetrahydrofurane (270 ml) to give a light yellow solution. The reaction mixture was cooled to 0-5° C. and methanesulfonyl chloride (8.43 g, 5.73 ml, 73.6 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 1 h to give a white suspension. The reaction mixture was filtered and washed with tetrahydrofurane (20 ml). Potassium 2-methyl-2-butoxide (1.7 M in toluene, 59 ml, 100 mmol) was added dropwise to the filtrate at 0-5° C. The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was poured into ethyl acetate and extracted with dilute aqueous hydrochloric acid (pH 5), water and brine. The organic layer was dried over MgSO4 and concentrated in vacuo to give a yellow oil which was further purified by flash chromatography (silica gel, heptane/ethyl acetate 4:1): yellow solid (19.5 g, 81%), MS (ISP): 259.9 ([{79Br}M-BOC+H]+), 261.9 ([{81Br}M-BOC+H]+).

1. customto give a light yellow solution
2. customto give a white suspension
3. filtrationThe reaction mixture was filtered
4. washwashed with tetrahydrofurane (20 ml)
5. stirringThe reaction mixture was stirred at room temperature for 30 min
6. extractionextracted with dilute aqueous hydrochloric acid (pH 5), water and brine
7. dry with materialThe organic layer was dried over MgSO4
8. concentrationconcentrated in vacuo
9. customto give a yellow oil which
10. customwas further purified by flash chromatography (silica gel, heptane/ethyl acetate 4:1)