聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯] → 2-Fluoro-5-piperidin-4-ylpyridine

HRID 12302

反应方程式

HRID 12302 反应方程式
[F:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.C([Li])CCC.O=[C:15]1[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]1.O>C(OCC)C>[F:1][C:2]1[N:3]=[CH:4][C:5]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[CH:6][CH:7]=1

参与物

6

反应物 4

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]HCID 735900N-叔丁氧羰基-4-哌啶酮HCID 27831682-氟-5-溴吡啶HCID 178418339正丁基锂

产物 1

HCID 230920092-Fluoro-5-piperidin-4-ylpyridine收率 52.7%

试剂、催化剂与溶剂 1

HCID 3283乙醚溶剂

反应条件

温度
-35 °C

实验过程

A solution of 2-fluoro-5-bromopyridine (7.69 g) in diethyl ether (160 ml) was cooled to −78° C., and into which n-butyl lithium (1,56M-hexane solution, 30 ml) was added dropwise at a temperature not higher than −70° C. After 15 minutes' stirring, tert-butyl 4-oxo-1-piperidinecarboxylate (8.7 g) was added. Temperature of the reaction liquid was raised to −35° C. and water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The organic layer was condensed under reduced pressure and isopropyl ether was added to the resulting residue. Whereupon precipitated crystals were recovered by filtration to provide the title compound (4.15 g). The filtrate was purified on column chromatography (hexane/ethyl acetate=3/1-2/1) to provide tert-butyl 4-(6-fluoro-3-pyridinyl)-4-hydroxy-tetrahydro-1(2H)-pyridinecarboxylate (1.25 g).

后处理

  1. customTemperature of the reaction liquid
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customcondensed under reduced pressure and isopropyl ether
  6. additionwas added to the resulting residue
  7. customWhereupon precipitated crystals
  8. filtrationwere recovered by filtration

来源与证据

ORD记录
ord-d993797223ee4d3ca68c621030b8b789
来源数据集
uspto-grants-2010_06
专利号
US07727998B2

关联笔记

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