反应详情

温度

-78 °C

To a solution of 7-fluoro-benzothiophene (0.22 g, 1.44 mmoles) in anhydrous tetrahydrofuran (10 ml) at −78° C. was added dropwise a solution of n-BuLi in hexane (1.6M, 0.9 ml, 1.44 mmoles). The reaction mixture was stirred at −78° C. for one hour, and then a solution of 3-formyl-3-(tetrahydro-pyran-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.3 g, 1.01 mmoles) in anhydrous tetrahydrofuran (5 ml) was then added. The reaction mixture was stirred at −78° C. for 3 hours, quenched with saturated aqueous ammonium chloride, and partitioned between ethyl acetate and saturated aqueous ammonium chloride solution. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (10 to 45% ethyl acetate in hexane) to yield 3-[(7-Fluoro-benzo[b]thiophen-2-yl)-hydroxy-methyl]-3-(tetrahydro-pyran-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a colorless semisolid (0.138 g, 30%). MS=450 [M+H]+.

1. stirringThe reaction mixture was stirred at −78° C. for 3 hours
2. customquenched with saturated aqueous ammonium chloride
3. custompartitioned between ethyl acetate and saturated aqueous ammonium chloride solution
4. washThe organic phase was washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel chromatography (10 to 45% ethyl acetate in hexane)