4-Methylmorpholine → [1-(2-Methoxyethyl)piperidin-4-yl]-methyl 4-(4-methylphenyl)piperazine-1-carboxylate

HRID 417961

반응식

HRID 417961 반응식
[C:1](=[O:24])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][O:12][CH3:13])[CH2:6][CH2:5]1.CN1CCOCC1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.Cl.Cl.[CH3:47][C:48]1[CH:53]=[CH:52][C:51]([N:54]2[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]2)=[CH:50][CH:49]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH3:47][C:48]1[CH:49]=[CH:50][C:51]([N:54]2[CH2:59][CH2:58][N:57]([C:1]([O:2][CH2:3][CH:4]3[CH2:5][CH2:6][N:7]([CH2:10][CH2:11][O:12][CH3:13])[CH2:8][CH2:9]3)=[O:24])[CH2:56][CH2:55]2)=[CH:52][CH:53]=1

참가 물질

8

반응물 5

HCID 79724-MethylmorpholineHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 831121-(p-Tolyl)piperazine dihydrochlorideHCID 57955470(1-(2-Methoxyethyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate2회

생성물 1

HCID 42635437[1-(2-Methoxyethyl)piperidin-4-yl]-methyl 4-(4-methylphenyl)piperazine-1-carboxylate수율 25.4%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

(1-(2-methoxyethyl)piperidin-4-yl)methanol (Intermediate 3, step 2; 1.73 g, 10.0 mmol) was dissolved in DCM (50 mL) and cooled to 0° C. NMM (1.21 mL, 11.0 mmol) and 4-nitrophenyl chloroformate (2.02 g, 10.0 mmol) were added. The reaction mixture was stirred at 0° C. for 15 minutes and then added to a solution of 4-(4-methylphenyl)piperazine dihydrochloride (2.62 g, 10.5 mmol) and DIPEA (6.10 mL, 35.0 mmol) in DMF (75 mL). The reaction mixture was stirred at room temperature for 4 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and then washed sequentially with 1M aq NaOH solution (6×100 mL), brine (100 mL), and then dried (MgSO4) and concentrated in vacuo. The residue was purified by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%). The resulting residue was dissolved in DCM (70 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give [1-(2-methoxyethyl)piperidin-4-yl]-methyl 4-(4-methylphenyl)piperazine-1-carboxylate (0.95 g, 25.4%) as a pale yellow oil.

후처리

  1. stirringThe reaction mixture was stirred at room temperature for 4 h
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in EtOAc (300 mL)
  4. washwashed sequentially with 1M aq NaOH solution (6×100 mL), brine (100 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by reverse phase chromatography (gradient
  8. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  9. dissolutionThe resulting residue was dissolved in DCM (70 mL)
  10. stirringstirred with solid K2CO3 for 20 minutes
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-ded7019769644b098fcc5fdbcb6ff272
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093248B2

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