1-(4-Fluorophenyl)piperazine → (1-Methylpiperidin-4-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate

HRID 417956

반응식

HRID 417956 반응식
[C:1](=[O:21])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]1.CCN(C(C)C)C(C)C.[F:31][C:32]1[CH:37]=[CH:36][C:35]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[CH:34][CH:33]=1>CN(C=O)C>[F:31][C:32]1[CH:33]=[CH:34][C:35]([N:38]2[CH2:43][CH2:42][N:41]([C:1]([O:2][CH2:3][CH:4]3[CH2:5][CH2:6][N:7]([CH3:10])[CH2:8][CH2:9]3)=[O:21])[CH2:40][CH2:39]2)=[CH:36][CH:37]=1

참가 물질

5

반응물 3

HCID 752601-(4-Fluorophenyl)piperazineHCID 81531DiisopropylethylamineHCID 57445006(1-Methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate2회

생성물 1

HCID 42609860(1-Methylpiperidin-4-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate수율 11.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

(1-Methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate (Intermediate 1; 4.99 g, 16.9 mmol) was dissolved in DMF (40 mL). DIPEA (5.90 mL, 33.9 mmol) and 4-(4-fluoro-phenyl)piperazine (3.21 g, 17.8 mmol) were added. The reaction mixture was stirred at room temperature for 3 h and then concentrated in vacuo. The residue was dissolved in EtOAc (400 mL) and then washed sequentially with 1 M aq NaOH solution (6×150 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (100 mL) and methyl isocyanate resin (1.0 g) was added. The reaction mixture was shaken for 14 h, filtered and then 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-methylpiperidin-4-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate (0.67 g, 11.8%) as a pale yellow oil.

후처리

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc (400 mL)
  3. washwashed sequentially with 1 M aq NaOH solution (6×150 mL), brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in DCM (100 mL)
  7. additionmethyl isocyanate resin (1.0 g) was added
  8. stirringThe reaction mixture was shaken for 14 h
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by reverse phase chromatography (gradient
  12. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  13. dissolutionThe resulting residue was dissolved in DCM (70 mL)
  14. stirringstirred with solid K2CO3 for 20 minutes
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-2e1b090cf6c0463e87ea83d24c77f027
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093248B2

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