反応 #43503

反応方程式

4-oxo-piperidine-1-carboxylic acid tert-butyl ester

2-bromo-4-fluoro-thiophenol

methyl lithium

tert-butyl lithium

→

crude product

4-(5-Fluoro-2-mercapto-phenyl)-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

溶媒

ethyl acetate

Water

tetrahydrofuran

反応条件

後処理

1. 1
   その他at −78° C.
2. 2
   温度to warm to rt
3. 3
   workup.STIRRINGstirred overnight
4. 4
   抽出The aqueous phase was extracted with ethyl acetate (50 mL) and saturated aqueous ammonium chloride (25 mL)
5. 5
   洗浄The organic phase was washed with saturated aqueous ammonium chloride (25 mL)
6. 6
   乾燥dried over magnesium sulfate
7. 7
   その他evaporated

実験手順

To a solution of 2-bromo-4-fluoro-thiophenol (6.0 g, 28.9 mmol) in dry tetrahydrofuran (TBF, 25 mL) at −78° C. was slowly added methyl lithium (1M in cumene/TBF, 28.9 mL, 28.9 mmol). After 30 min at −78° C., tert-butyl lithium (1.7 M in THF, 39.9 mL, 63.8 mmol) was added and the reaction mixture was stirred 30 min at −78° C. A solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (5.77 g, 28.9 mmol) in THE (20 mL) was added and the reaction mixture was allowed to warm to rt and stirred overnight. Water (50 mL) and ethyl acetate (25 mL) were added, and organic phase was discarded. The aqueous phase was extracted with ethyl acetate (50 mL) and saturated aqueous ammonium chloride (25 mL). The organic phase was washed with saturated aqueous ammonium chloride (25 mL) and dried over magnesium sulfate, and evaporated to afford the crude product. The crude product was purified by flash chromatography on silica gel (eluent: An increasing amount (0-20%) of ethyl acetate in heptane). Yield: 4.67 g (49%).

出典