反应详情

温度

-78 °C

A solution of 2-(5-bromo-2-fluoro-phenyl)[1,3]dithiane (19 g, 64.84 mmol) in THF (100 ml) was added to a degassed and stirred 2 M solution of LDA (32.42 ml, 64.84 mmol) in THF dry (150 ml) at −78° C. and the reaction was carried out at −20° C. for 30 min. The reaction was cooled down again to −78° C. and tert-butyl 4-oxo-1-piperidinecarboxylate (13.03 g, 65.5 mmol) in THF (100 ml) was added dropwise. After 30 min, a further portion of tert-butyl 4-oxo-1-piperidinecarboxylate was added (0.5 g, 0.25 mmol). After 1 h, the reaction mixture was poured into a saturated NH4Cl solution (200 ml) and extracted with AcOEt. The combined organic fractions were washed with water (100 ml), brine (100 ml), dried over Na2SO4, then filtered and evaporated to give a yellow oil. The crude product was purified by column chromatography (AcOEt/hexane 30/70) to give 4-[2-(5-bromo-2-fluoro-phenyl)-[1,3]dithian-2-yl]-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester as a white solid (13 g).

1. customa degassed
2. customdry (150 ml) at −78° C.
3. waitAfter 30 min
4. waitAfter 1 h
5. extractionextracted with AcOEt
6. washThe combined organic fractions were washed with water (100 ml), brine (100 ml)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customevaporated
10. customto give a yellow oil
11. customThe crude product was purified by column chromatography (AcOEt/hexane 30/70)