1-Bromo-3-fluorobenzene → HCID 57893715、化合物

HRID 1821992ノート

反応式

HRID 1821992 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([OH:14])[CH2:10][C@@H:9]1[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21](F)[CH:20]=1>CN1CCCC1=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([O:14][C:21]2[CH:22]=[CH:23][CH:24]=[C:19]([Br:18])[CH:20]=2)[CH2:10][C@@H:9]1[CH3:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 140821-Bromo-3-fluorobenzeneHCID 24758Sodium hydrideHCID 450974411-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4R)-(9CI)

生成物 1

HCID 57893715HCID 57893715、化合物収率 46%

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
100 °C

実験手順

Dissolve 4-hydroxy-trans-2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 1 (preparation 2, 3.03 g, 14.07 mmol) in 1-methyl-2-pyrrolidinone (50 mL), treat with 95% sodium hydride (0.33 g, 12.93 mmol), stir and beat at 70° C. After 1 hr., add 1-bromo-3-fluoro-benzene (1.73 mL, 15.5 mmol), stir, and heat at 100° C. After 16 hr., cool to ambient temperature and quench with water (100 mL). Extract with 4:1 hexane:ethyl acetate (2×100 mL), combine the organic layers and wash with aqueous NaCl solution (75 mL), dry over sodium sulfate, filter and concentrate. Purify the residue by silica gel flash chromatography eluting with 4:1 hexanes:ethyl acetate to obtain of the title compound (2.42 g, 46%). 1H NMR (CDCl3): 7.1 (m, 3H), 6.8 (m, 1H), 4.55 (m, 1H), 4.5 (m, 1H), 4.1 (m, 1H), 2.95 (m, 1H), 2.1 (m, 1H), 1.95 (m, 1H), 1.7 (m, 1H), 1.5 (m, 1H), 1.45 (s, 9H), 1.2 (d, 3H).

後処理

  1. dissolutionDissolve
  2. customat 70° C
  3. stirringstir
  4. waitAfter 16 hr
  5. temperature, cool to ambient temperature
  6. customquench with water (100 mL)
  7. extractionExtract with 4:1 hexane
  8. washwash with aqueous NaCl solution (75 mL)
  9. dry with materialdry over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify the residue by silica gel flash chromatography
  13. washeluting with 4:1 hexanes

出典と根拠

ORDレコード
ord-d694c2ccbfe04f5db5b8dc16d338c51e
出典データセット
uspto-grants-2009_10
特許番号
US07608629B2

反応ノート

読み込み中…