Ammonium Hydroxide → 4-Methoxy-7-cyanoindole

HRID 1368166

반응식

HRID 1368166 반응식
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9](Br)=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2.[C:13]([Cu])#[N:14].[OH-].[NH4+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([C:13]#[N:14])=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2

참가 물질

5

반응물 3

HCID 14923Ammonium HydroxideHCID 36954997-Bromo-4-methoxy-1H-indoleHCID 178418546HCID 178418546, 화합물

생성물 1

HCID 226330844-Methoxy-7-cyanoindole

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
165 °C

실험 절차

To an oven dried 500 ml round bottom flask at rt. was charged with 4-methoxy-7-bromo-indole intermediate 5 (12.8 g, 56.6 mmol) and dry DMF (120 ml), followed by CuCN (25.3 g, 283 mmol). The reaction mixture was refluxed at 165° C. for 16 hr. After cooling to rt., the mixture was slowly added ammonium hydroxide (100 ml), stirred for 10 min, concentrated in vacuo to ˜50 ml and diluted with CHCl3 (250 ml). The organic mixture was washed with H2O (250 ml), and the aqueous layer back extracted with CHCl3 (2×200 ml). The combined organic extracts were filtered through a filter paper to remove some solids, and washed again with H2O (100 ml) and brine (100 ml), and then dried (MgSO4). After evaporation in vacuo, the residue was purified by flash column chromatography (10% EtOAc/Hexane (250 ml), then 25% EtOAc/Hexanes (1250 ml)) to afford 4-methoxy-7-cyanoindole intermediate 35 (8.0 g, 82%) as yellow solids. 1H NMR: (CDCl3) δ 8.73 (b s, 1H), 7.50 (d, J=8.3 Hz), 7.22 (app t, J=2.8 Hz, 1H), 6.73 (dd, J=2.3, 3.2 Hz, 1H), 6.58 (d, J=8.3 Hz, 1H), 4.01 (s, 3H); LC/MS: (ES+) m/z (M+H)+=173, HPLC (YMC C18 S7 3×50 mm, Flow Rate 4 ml/min, Gradient Time 3 min) Rt=1.700.

후처리

  1. customTo an oven dried 500 ml round bottom flask at rt
  2. temperatureAfter cooling to rt
  3. concentrationconcentrated in vacuo to ˜50 ml
  4. additiondiluted with CHCl3 (250 ml)
  5. washThe organic mixture was washed with H2O (250 ml)
  6. extractionthe aqueous layer back extracted with CHCl3 (2×200 ml)
  7. filtrationThe combined organic extracts were filtered through a filter paper
  8. customto remove some solids
  9. washwashed again with H2O (100 ml) and brine (100 ml)
  10. dry with materialdried (MgSO4)
  11. customAfter evaporation in vacuo
  12. customthe residue was purified by flash column chromatography (10% EtOAc/Hexane (250 ml)

출처 및 근거

ORD 기록
ord-eec2410596554307b2c30747acf05a09
출처 데이터셋
uspto-grants-2003_06
특허 번호
US06573262B2

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