Reaktion #43503

Reaktionsgleichung

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

Lösungsmittel

ethyl acetate

Water

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeat −78° C.
2. 2
   Temperaturto warm to rt
3. 3
   workup.STIRRINGstirred overnight
4. 4
   ExtraktionThe aqueous phase was extracted with ethyl acetate (50 mL) and saturated aqueous ammonium chloride (25 mL)
5. 5
   WaschenThe organic phase was washed with saturated aqueous ammonium chloride (25 mL)
6. 6
   Trocknendried over magnesium sulfate
7. 7
   Sonstigeevaporated

Vorschrift

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%).

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