3-Bromoanisole → 1-Benzyl-3-(3-methoxyphenyl)piperidin-3-ol

HRID 1633536

反応式

HRID 1633536 の反応式
[Mg].Br[C:3]1[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[CH:7][CH:8]=1.[CH2:11]([N:18]1[CH2:23][CH2:22][CH2:21][C:20](=[O:24])[CH2:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1>[CH2:11]([N:18]1[CH2:23][CH2:22][CH2:21][C:20]([C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[CH:4]=2)([OH:24])[CH2:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

参加物

5

反応物 3

HCID 169713-BromoanisoleHCID 966503-Piperidinone, 1-(phenylmethyl)-HCID 5462224Magnesium

生成物 1

HCID 136950931-Benzyl-3-(3-methoxyphenyl)piperidin-3-ol収率 81.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
50 °C

実験手順

To a suspension of magnesium (7.8 g, 325 mmol) in THF (120 mL) at room temperature under a nitrogen atmosphere was added a solution of 3-bromoanisole (37.5 mL, 296 mmol) in THF (60 mL) over 10 min. The resulting mixture was stirred at 50° C. for 4 hours and was cooled to room temperature. To the mixture was added a solution an N-benzyl-3-piperidinone (30.0 g, 159 mmol) in THF (50 mL). The reaction was stirred at room for 10 hours. The mixture was poured slowly over ice-water (100 mL) and the aqueous layer was washed with EtOAc (3×50 mL). The combined organic extracts were dried (MgSO4) and concentrated. The crude residue was purified by flash chromatography with hexanes/EtOAc (3:1) to afford 38.4 g of 1-benzyl-3-(3-methoxy-phenyl)-piperidin-3-ol 1HNMR (400 MHz, CDCl3) δ 7.31-7.20 (comp, 6H), 7.09 (s, 1H), 7.01 (d, 1H), 6.79 (d, 1H), 4.01-3.96 (br, 1H), 3.79 (s, 3H), 3.58 (s, 2H), 2.91 (d, 1H), 2.74 (d, 1H), 2.32 (d, 1H), 2.09-1.82 (comp, 2H), 1.81-1.61 (comp, 3H); MS (M+1) 298.2.

後処理

  1. temperaturewas cooled to room temperature
  2. stirringThe reaction was stirred at room for 10 hours
  3. washthe aqueous layer was washed with EtOAc (3×50 mL)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash chromatography with hexanes/EtOAc (3:1)

出典と根拠

ORDレコード
ord-0a1bc6c1fee446da9ad41593ddbae45f
出典データセット
uspto-grants-2003_01
特許番号
US06503905B1

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