Methyl iodide → tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

HRID 474895

反応式

HRID 474895 の反応式
Cl.[Br:2][C:3]1[CH:4]=[C:5]([NH:9]N)[CH:6]=[CH:7][CH:8]=1.O=[C:12]1[CH2:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:13]1.[CH3:26]C(OC(OC(OC(C)(C)C)=O)=O)(C)C.C([O-])([O-])=O.[K+].[K+].[H-].[Na+].CI>CN(C=O)C.O.O.CC(O)C.CCO>[Br:2][C:3]1[CH:8]=[CH:7][C:6]2[C:18]3[CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:13][C:12]=3[N:9]([CH3:26])[C:5]=2[CH:4]=1

参加物

11

反応物 6

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 337573-Bromophenylhydrazine hydrochlorideHCID 90495Di-tert-butyl dicarbonateHCID 1512679N-Boc-hexahydro-1H-azepin-4-one

生成物 1

HCID 58093439tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate収率 6.1%

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒HCID 21889133Propan-2-ol--water (1/1)溶媒

反応条件

温度
25 °C

実験手順

A solution of 3-bromophenylhydrazine hydrochloride (15.75 g, 70.33 mmol) and tert-butyl 4-oxoazepane-1-carboxylate (15.05 g, 70.33 mmol) in 15:2 EtOH/(12 N HCl solution) (102 mL) was stirred at reflux overnight. The solution was concentrated under reduced pressure to afford a red oil. Boc2O (46.00 g, 211.0 mmol) was added to a suspension of the red oil and K2CO3 (29.12 g, 211.0 mmol) in 1:1 H2O/i-PrOH (180 mL), and the resulting suspension was stirred at 25° C. for 2 h. H2O was added, and the resulting suspension was filtered. The filtrate was extracted with CH2Cl2, and the combined extracts were dried over Na2SO4. The resulting solution was concentrated under reduced pressure, and flash chromatography (silica gel, hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a viscous red oil. NaH (60% dispersion in oil, 5.626 g, 140.7 mmol) was added to a solution of the viscous red oil in DMF (60 mL) under N2, and the resulting suspension was stirred at 25° C. for 45 min. MeI (6.6 mL, 106 mmol) was added to the suspension, and the resulting suspension was stirred at 25° C. for 2 h. H2O was added, and the aqueous solution was extracted with CH2Cl2. The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (silica gel, hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (1.62 g, 6%) as a yellow foam and the title compound (2.80 g, 9%) as a white foam: 1H NMR (300 MHz, CDCl3) δ 8.28 (br s, 0.5H), 8.21 (br s, 0.5H), 7.34 (dd, J=8.4, 1.5 Hz, 1H), 7.30-7.22 (1H, overlapping with solvent), 3.85-3.63 (m, 4H), 3.39-3.32 (m, 2H), 2.99-2.91 (m, 2H), 1.68 (s, 4.5H), 1.67 (s, 4.5H), 1.48 (s, 9H).

後処理

  1. temperatureat reflux overnight
  2. concentrationThe solution was concentrated under reduced pressure
  3. customto afford a red oil
  4. filtrationthe resulting suspension was filtered
  5. extractionThe filtrate was extracted with CH2Cl2
  6. dry with materialthe combined extracts were dried over Na2SO4
  7. concentrationThe resulting solution was concentrated under reduced pressure, and flash chromatography (silica gel, hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100)
  8. customafforded a viscous red oil
  9. stirringthe resulting suspension was stirred at 25° C. for 45 min
  10. stirringthe resulting suspension was stirred at 25° C. for 2 h
  11. extractionthe aqueous solution was extracted with CH2Cl2
  12. washThe combined extracts were washed with brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-cb02382650d241f9b04df4b3eecafe5c
出典データセット
uspto-grants-2014_01
特許番号
US08637501B2

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