Benzyl Bromide → 1-tert-Butyl 4-ethyl 4-benzylpiperidine-1,4-dicarboxylate

HRID 2179808ノート

反応式

HRID 2179808 の反応式
C(N(C(C)C)CC)(C)C.[N:10]1([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15][CH2:14][CH:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][CH2:11]1.[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1COCC1>[CH2:28]([C:13]1([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][CH2:11][N:10]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:15][CH2:14]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

参加物

5

反応物 3

HCID 7498Benzyl BromideHCID 81531DiisopropylethylamineHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

生成物 1

HCID 162182711-tert-Butyl 4-ethyl 4-benzylpiperidine-1,4-dicarboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-75 °C

実験手順

Diisopropyl ethylamine (6.5 ml) in dry THF (25 ml) cooled the contents to about −10° C. then N-butyl lithium (1.6 M, 23 ml) was added drop wise under nitrogen atmosphere and maintain the same temperature for about 45 minutes and cooled to about −75° C. for about 15 minutes then 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (step 1, 5 g) in THF (30 ml) was added and stirred for about 30 minutes then increase the reaction temperature to −35° C. and stirred for about 45 minutes and again cooled to −75° C. then benzyl bromide (3.5 g in 20 ml THF) was added drop wise and slowly allowed the reaction to room temperature and stirred the reaction for about 12 hours. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with sat. NaHCO3 followed by brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 3% ethyl acetate in hexane as eluent to furnish the title compound as a light yellow colour liquid. 1H NMR (300 MHz, CDCl3): 1.16-1.18 (t, 3H); 1.44 (s, 9H); 2.07-2.11 (m, 2H); 2.28 (s, 1H); 2.82 (s, 2H); 2.92-2.95 (m, 1H); 3.46-3.52 (m, 3H); 4.09-4.11 (m, 2H); 7.03-7.06 (m, 2H); 7.23-7.24 (m, 3H); ES Mass: 370 (100%) [M+Na].

後処理

  1. temperaturemaintain the same temperature for about 45 minutes
  2. temperaturethen increase the reaction temperature to −35° C.
  3. stirringstirred for about 45 minutes
  4. temperatureagain cooled to −75° C.
  5. customthe reaction to room temperature
  6. stirringstirred
  7. customthe reaction for about 12 hours
  8. customAfter completion of the reaction (monitored by TLC)
  9. customthe reaction mixture was quenched with saturated ammonium chloride
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed with sat. NaHCO3
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-ca23bd4e496548fba2ec9abf6f70c595
出典データセット
uspto-grants-2015_06
特許番号
US09067966B2

反応ノート

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