Water → 2-Fluoro-5-piperidin-4-ylpyridine

HRID 12302

反応式

HRID 12302 の反応式
[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

参加物

6

反応物 4

HCID 962WaterHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 27831685-Bromo-2-fluoropyridineHCID 178418339Butyllithium

生成物 1

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

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒

反応条件

温度
-35 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d993797223ee4d3ca68c621030b8b789
出典データセット
uspto-grants-2010_06
特許番号
US07727998B2

関連ノート

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