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Water → 1-(1-(2-Ethyl-5-methoxy-4-nitrophenyl)piperidin-4-yl)-4-(methylsulfonyl)piperazine

HRID 419598
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HRID 419598 반응식
[CH2:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([O:12][CH3:13])=[CH:5][C:4]=1F)[CH3:2].Cl.Cl.[CH3:17][S:18]([N:21]1[CH2:26][CH2:25][N:24]([CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH2:23][CH2:22]1)(=[O:20])=[O:19].C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[CH2:1]([C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([O:12][CH3:13])=[CH:5][C:4]=1[N:30]1[CH2:29][CH2:28][CH:27]([N:24]2[CH2:25][CH2:26][N:21]([S:18]([CH3:17])(=[O:20])=[O:19])[CH2:22][CH2:23]2)[CH2:32][CH2:31]1)[CH3:2]
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참가 물질

6

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 594528471-Ethyl-2-fluoro-4-methoxy-5-nitrobenzeneHCID 666497911-(Methylsulfonyl)-4-(4-piperidinyl)piperazine dihydrochloride

생성물 1

HCID 594529781-(1-(2-Ethyl-5-methoxy-4-nitrophenyl)piperidin-4-yl)-4-(methylsulfonyl)piperazine수율 56.2%

시약·촉매·용매 1

HCID 679
Dimethyl Sulfoxide
용매

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온도
90 °C

실험 절차

A mixture of 1-ethyl-2-fluoro-4-(methyloxy)-5-nitrobenzene (Example 187, step C) (0.93 g, 4.67 mmol), 1-(methylsulfonyl)-4-(4-piperidinyl)piperazine (Example 204, step C) (1.16 g, 4.67 mmol) and K2CO3 (0.774 g, 5.60 mmol) in DMSO (20 mL) was heated at 90° C. for 48 h. The reaction had not progressed sufficiently so the reaction was then heated at 120° C. for an additional 4 h. The reaction was cooled to rt, poured into H2O and extracted with DCM. Some saturated brine solution was added and the resultant was exhaustively extracted with DCM. The combined organics were washed with H2O then dried over MgSO4. The resultant solution was concentrated onto silica and purified by flash chromatography to afford 1-{1-[2-ethyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-4-(methylsulfonyl)piperazine (1.12 g, 56%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.73-7.80 (m, 1H), 6.75 (s, 1H), 3.91 (s, 3H), 3.23-3.30 (m, 1H), 3.05-3.19 (m, 3H), 2.87 (s, 2H), 2.70-2.84 (m, 2H), 2.53-2.67 (m, 5H), 1.77-1.94 (m, 2H), 1.48-1.67 (m, 2H), 1.19 (t, J=7.42 Hz, 3H).

후처리

  1. temperaturewas then heated at 120° C. for an additional 4 h
  2. temperatureThe reaction was cooled to rt
  3. extractionextracted with DCM
  4. additionSome saturated brine solution was added
  5. extractionthe resultant was exhaustively extracted with DCM
  6. washThe combined organics were washed with H2O
  7. dry with materialthen dried over MgSO4
  8. concentrationThe resultant solution was concentrated onto silica
  9. custompurified by flash chromatography

출처 및 근거

ORD 기록
ord-bd242b5d9fd548ddbf0125fad5e77dc9
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093239B2

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