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

HRID 1751064

반응식

HRID 1751064 반응식
[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

참가 물질

5

반응물 3

HCID 80061-Bromo-3-chloropropaneHCID 21711Methyl 3-(1H-indol-3-yl)propanoateHCID 24758Sodium hydride2회

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
55 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-fbff82ca74b243a2b27329d672660f54
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156840B2

연결된 노트

불러오는 중…