2-Butene, 1-bromo-3-methyl- → 1-Benzyl 3-ethyl 3-(3-methylbut-2-en-1-yl)piperidine-1,3-dicarboxylate

HRID 2059828노트

반응식

HRID 2059828 반응식
[N:1]1([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:6][CH2:5][CH2:4][CH:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:33][CH:34]=[C:35]([CH3:37])[CH3:36]>C1COCC1>[CH3:36][C:35]([CH3:37])=[CH:34][CH2:33][C:3]1([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:4][CH2:5][CH2:6][N:1]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:2]1

참가 물질

5

반응물 3

HCID 700922-Butene, 1-bromo-3-methyl-HCID 2724254Sodium bis(trimethylsilyl)amideHCID 17999271Benzyl ethyl piperidine-1,3-dicarboxylate

생성물 1

HCID 598689181-Benzyl 3-ethyl 3-(3-methylbut-2-en-1-yl)piperidine-1,3-dicarboxylate수율 94.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
-78 °C

실험 절차

To a solution of 1-benzyl 3-ethyl piperidine-1,3-dicarboxylate (120.0 g, 0.412 mol) in THF (400 ml) cooled at −78° C. was added dropwise 270 mL of sodium bis(trimethylsilyl)amide solution (1M solution in THF from Aldrich, cat #:245585) over 2 h. The mixture was stirred at −78° C. for additional 1 h. Then 1-bromo-3-methylbut-2-ene (Aldrich cat #: 249904) (71 mL, 0.62 mol) was added slowly over 1 h. The mixture was stirred at −78° C. for 30 min, and allowed to warm to r.t. and stirred for an additional 3 h. The reaction mixture was quenched with 1N HCl aq. solution. Most of THF was removed under reduced pressure. The residue was extracted with ethyl acetate. The combined extracts were washed with sat. aq. NaHCO3 and brine, then dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on a silica gel column with 10˜20% ethyl acetate in hexane to yield the desired product (140 g, 94%). LC/MS: m/e=332.2 (M+H)+.

후처리

  1. stirringThe mixture was stirred at −78° C. for 30 min
  2. temperatureto warm to r.t.
  3. stirringstirred for an additional 3 h
  4. customThe reaction mixture was quenched with 1N HCl aq. solution
  5. customMost of THF was removed under reduced pressure
  6. extractionThe residue was extracted with ethyl acetate
  7. washThe combined extracts were washed with sat. aq. NaHCO3 and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude residue was purified by flash column chromatography on a silica gel column with 10˜20% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-5b41bce202ef4087ab36461c7ce14e44
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08278318B2

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