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

HRID 272918ノート

反応式

HRID 272918 の反応式
[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

参加物

8

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒3 回HCID 14798Sodium Hydroxide溶媒HCID 15413tert-Butyl methyl ether溶媒

反応条件

温度
75 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-204b467618604aaaa0e043413b978fee
出典データセット
uspto-grants-2008_11
特許番号
US07456164B2

反応ノート

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