p-Bromochlorobenzene → 4-(4-Chlorophenyl)-1-(3-methoxybenzyl)piperidin-4-ol

HRID 2167509ノート

反応式

HRID 2167509 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.C([Li])CCC.[CH3:14][O:15][C:16]1[CH:17]=[C:18]([CH:27]=[CH:28][CH:29]=1)[CH2:19][N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1>O1CCCC1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:23]2([OH:26])[CH2:22][CH2:21][N:20]([CH2:19][C:18]3[CH:27]=[CH:28][CH:29]=[C:16]([O:15][CH3:14])[CH:17]=3)[CH2:25][CH2:24]2)=[CH:3][CH:4]=1

参加物

5

反応物 3

HCID 7806p-BromochlorobenzeneHCID 119595401-[(3-Methoxyphenyl)methyl]piperidin-4-oneHCID 178418339Butyllithium

生成物 1

HCID 667639424-(4-Chlorophenyl)-1-(3-methoxybenzyl)piperidin-4-ol収率 53.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To 1-bromo-4-chlorobenzene (397 mg, 2.07 mmol) in tetrahydrofuran (10 mL), at −78° C., was added n-butyllithium (0.91 mL of a 2.5 M solution in hexanes, 2.3 mmol) dropwise. After 0.5 h, a solution of the ketone (500 mg, 2.28 mmol) from Step B above in tetrahydrofuran (5 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 1.5 h and then warmed to 0° C. After 1 h, the reaction mixture was quenched with saturated ammonium chloride (5 mL) and warmed to ambient temperature. The mixture was diluted with ethyl acetate (50 mL) and washed with saturated ammonium chloride (20 mL), water (20 mL), brine (20 mL), dried over sodium sulfate and concentrated in vacuo. Purification by silica gel chromatography (5% ethyl acetate/methylene chloride to ethyl acetate) gave 4-(4-chlorophenyl)-1-(3-methoxybenzyl)piperidin-4-ol (370 mg, 53%) as a colorless oil: 1H NMR (DMSO-d6, 500 MHz) δ 7.50 (d, J=8.5 Hz, 2H), 7.35 (d, J=8.5 Hz, 2H), 7.24-7.21 (m, 1H), 6.90-6.89 (m, 2H), 6.81-6.79 (m, 1H), 4.87 (s, 1H), 3.74 (s, 3H), 3.47 (s, 2H), 2.61-2.59 (m, 2H), 2.43-2.38 (m, 2H), 1.94-1.87 (m, 2H), 1.57-1.54 (m, 2H).

後処理

  1. temperaturewarmed to 0° C
  2. waitAfter 1 h
  3. customthe reaction mixture was quenched with saturated ammonium chloride (5 mL)
  4. temperaturewarmed to ambient temperature
  5. additionThe mixture was diluted with ethyl acetate (50 mL)
  6. washwashed with saturated ammonium chloride (20 mL), water (20 mL), brine (20 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography (5% ethyl acetate/methylene chloride to ethyl acetate)

出典と根拠

ORDレコード
ord-7d8f8a67716f4b749376ef8648543f03
出典データセット
uspto-grants-2015_06
特許番号
US09045468B2

反応ノート

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