Sodium hydride → 4-[4-(1-Cyclopentylpiperidin-4-yloxy)phenyl]tetrahydropyran-4-carbonitrile

HRID 272918노트

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HRID 272918 반응식
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[H-].[Na+].[CH:18]1([N:23]2[CH2:28][CH2:27][CH:26](OS(C)(=O)=O)[CH2:25][CH2:24]2)[CH2:22][CH2:21][CH2:20][CH2:19]1>CN(C=O)C.CC(OC)(C)C.O.[OH-].[Na+]>[CH:18]1([N:23]2[CH2:28][CH2:27][CH:26]([O:1][C:2]3[CH:7]=[CH:6][C:5]([C:8]4([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)=[CH:4][CH:3]=3)[CH2:25][CH2:24]2)[CH2:19][CH2:20][CH2:21][CH2:22]1

참가 물질

8

반응물 3

HCID 24758Sodium hydrideHCID 230916094-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrileHCID 86601898Methanesulfonic acid 1-cyclopentyl-piperidin-4-yl ester

생성물 1

HCID 598374144-[4-(1-Cyclopentylpiperidin-4-yloxy)phenyl]tetrahydropyran-4-carbonitrile수율 13%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매3회HCID 14798Sodium Hydroxide용매HCID 15413tert-Butyl methyl ether용매

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온도
75 °C

실험 절차

4-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile (459 mg, 2.26 mmol) in DMF (2 ml) was added to a solution of NaH (100 mg, 2.5 mmol) in DMF (2 ml) at room temperature under N2. The reaction was stirred for 1 hr and a solution of methanesulfonic acid 1-cyclopentyl-piperidin-4-yl ester (447 mg, 1.81 mmol) in DMF (1.3 ml) was slowly added. The reaction was heated to 75° C. and stirred for 6 hrs. The reaction was allowed to cool to room temperature and diluted with TBME (20 ml), water (10 ml) and 5M NaOH solution (10 ml). The organic layer was washed with 2.5M NaOH (2×20 ml), brine (2×20 ml), dried over MgSO4, filtered and concentrated in vacuo. The crude reaction was purified by successive column chromatography, eluting with DCM:MeOH:NH3 (98:1:1) to give the title compound as a pale yellow solid (81 mg, 13%). 1H NMR (400 MHz, CDCl3) δ 7.37 (d, 2H), 6.93 (d, 2H), 4.36 (m, 1H), 4.11-4.04 (m, 2H), 3.89 (td, 2H), 2.91-2.77 (m, 2H), 2.67-2.25 (m, 2H), 2.15-1.99 (m, 7H), 1.95-1.81 (m, 4H), 1.78-1.64 (m, 2H), 1.62-1.39 (m, 4H).

후처리

  1. stirringstirred for 6 hrs
  2. temperatureto cool to room temperature
  3. washThe organic layer was washed with 2.5M NaOH (2×20 ml), brine (2×20 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude reaction
  8. customwas purified by successive column chromatography
  9. washeluting with DCM:MeOH:NH3 (98:1:1)

출처 및 근거

ORD 기록
ord-204b467618604aaaa0e043413b978fee
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07456164B2

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