1-Bromo-3-chloropropane → methyl 3-(1-(3-chloropropyl)-1H-indol-3-yl)propanoate

HRID 1751064

反応式

HRID 1751064 の反応式
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:4]1.Br[CH2:19][CH2:20][CH2:21][Cl:22]>CN(C)C=O>[Cl:22][CH2:21][CH2:20][CH2:19][N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:4]1

参加物

5

反応物 3

HCID 80061-Bromo-3-chloropropaneHCID 21711Methyl 3-(1H-indol-3-yl)propanoateHCID 24758Sodium hydride2 回

生成物 1

HCID 58046806methyl 3-(1-(3-chloropropyl)-1H-indol-3-yl)propanoate収率 83.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
55 °C

実験手順

Sodium hydride (60% dispersion) (236 mg, 5.91 mmol, 1.2 equiv) was slowly added to a cold mixture of methyl 3-(1H-indol-3-yl)propanoate (2 g, 4.92 mmol, 1 equiv) in N,N-dimethylformamide. After all the sodium hydride has reacted, 1-bromo-3-chloropropane (1.94 ml, 19.68 mmol, 4 equiv) was added and the reaction stirred at 55° C. for 16 h. Upon cooling the reaction was partitioned between water and ethyl acetate. The organic layer was further washed with 1N hydrogen chloride, brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was purified using the Biotage flash chromatography system (SNAP 50 g cartridge, Rf=0.5, gradient—1%-10% ethyl acetate in hexanes) to afford the title compound as a yellow oil (1.154 g, 83%); 1H NMR (400 MHz, DMSO-d6): δ 2.12-2.27 (m, 2H); 2.65-2.70 (m, 2H); 2.93-2.98 (m, 2H); 3.38-3.54 (m, 2H); 3.58 (s, 3H); 4.08-4.12 (m, 2H); 4.21-4.25 (m, 2H); 7.02 (t, 1H, J=7.6 Hz); 7.12-7.15 (m, 2H); 7.43 (dd, 1H, J=3.2 and 2.8 Hz); 7.52-7.55 (m, 1H); MS for C15H18ClNO2 m/z 280 (M+H)+.

後処理

  1. temperatureUpon cooling the reaction
  2. customwas partitioned between water and ethyl acetate
  3. washThe organic layer was further washed with 1N hydrogen chloride, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified

出典と根拠

ORDレコード
ord-fbff82ca74b243a2b27329d672660f54
出典データセット
uspto-grants-2015_10
特許番号
US09156840B2

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