Piperazine → N-[2-(6-Methoxymethoxy-2,5,7,8-tetramethylchroman-2-yl)ethyl]piperazine

HRID 131060노트

반응식

HRID 131060 반응식
C1(C)C=CC(S(O[CH2:11][CH2:12][C:13]2([CH3:30])[CH2:22][CH2:21][C:20]3[C:15](=[C:16]([CH3:29])[C:17]([CH3:28])=[C:18]([O:24][CH2:25][O:26][CH3:27])[C:19]=3[CH3:23])[O:14]2)(=O)=O)=CC=1.[NH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.CCCCCC.C(OCC)(=O)C.C(Cl)(Cl)Cl.CO>C1(C)C=CC=CC=1>[CH3:27][O:26][CH2:25][O:24][C:18]1[C:19]([CH3:23])=[C:20]2[C:15](=[C:16]([CH3:29])[C:17]=1[CH3:28])[O:14][C:13]([CH2:12][CH2:11][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)([CH3:30])[CH2:22][CH2:21]2

참가 물질

6

반응물 4

HCID 4837Piperazine2회HCID 21226206Ethyl acetate hexaneHCID 21584188Chloroform methanolHCID 224173562-(6-Methoxymetoxy-2,5,7,8-tetramethylchroman-2-yl)ethyl p-toluenesulfonate2회

생성물 1

HCID 69221526N-[2-(6-Methoxymethoxy-2,5,7,8-tetramethylchroman-2-yl)ethyl]piperazine

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

2-(6-Methoxymetoxy-2,5,7,8-tetramethylchroman-2-yl)ethyl p-toluenesulfonate (compound 4) (16.01 g, 35.7 mmol) was diluted in 200 mL of toluene, and piperazine (6.15 g, 71.4 mmol) was added to it, as shown in FIG. 5. The reaction solution was heated at reflux. TLC (silica gel 60 F254 plates; hexane:ethyl acetate (2:1) and chloroform:methanol (4:1)) indicated the reaction to be complete after 2.5 hours, and therefore, it was worked-up as follows: The reaction solution was cooled to room temperature (RT) which caused residual piperazine to precipitate out, and the piperazine was removed by filtration. The filter cake was rinsed with toluene, and this rinsing was combined with the filtrate. The filtrate was concentrated to an oil which weighed 15.79 g. The oil was diluted with chloroform (25 mL), and it was decanted onto a silica gel column (230-400 mesh, 60 Å) that had been prepared with chloroform:methanol (6:1) slurry. The flash column bed measured ˜5 cm×30 cm. The flash column was eluted with the following mobile phase systems: 1) CHCl3:MeOH (6:1); 3 L; -collected 40ט30 mL fractions, followed by 8ט100 mL fractions; 2) CHCl3:MeOH (2:1); 1.8 L; -collected 4×200 mL fractions, followed by 2×400 mL fractions; and 3) CHCl3:MeOH (1:1); 0.8 L; -collected 2×400 mL fractions. Based upon the TLC results of each fraction, appropriate fractions were combined and concentrated to a clear oil which weighed 10.70 g. The compound was characterized by NMR and MS as follows: 1) C-NMR (CDCl3): 12.25, 12.80, 13.68, 20.99, 24.42, 32.07, 36.59, 46.48, 54.42, 55.19, 57.88, 74.35, 99.89, 117.69, 123.28, 126,51, 128.45, 147.25, 148.16 ppm; 2) H-NMR (CDCl3): 1.23 (s, 3H), 1.78 (m, 5H), 2.05 (s, 3H), 2.12 (s, 3H), 2.16 (s, 3H), 2.39 (b, 4H), 2.48 (t, 2H), 2.57 (t, 2H), 286 (t, 4H), 3.59 (s, 3H), 4.82 (s, 2H) ppm; and 3) MS (ESI): 363.3 [M+H]+.

후처리

  1. temperatureThe reaction solution was heated
  2. temperatureat reflux
  3. customthe reaction
  4. customto precipitate out
  5. customthe piperazine was removed by filtration
  6. washThe filter cake was rinsed with toluene
  7. concentrationThe filtrate was concentrated to an oil which
  8. additionThe oil was diluted with chloroform (25 mL), and it
  9. customwas decanted onto a silica gel column (230-400 mesh, 60 Å) that
  10. customhad been prepared with chloroform:methanol (6:1) slurry
  11. washThe flash column was eluted with the following mobile phase systems
  12. customTLC results of each fraction, appropriate fractions
  13. concentrationconcentrated to a clear oil which

출처 및 근거

ORD 기록
ord-c58fc38a6d224b1992ea40ff155317f4
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384558B2

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