Water → 1-(3,4-Dimethoxy-benzyl)-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-benzo[c]azepine

HRID 2414817Notes

Reaction equation

HRID 2414817 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][C:12]([NH:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[CH:19]=2)=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O=P(Cl)(Cl)Cl.[BH4-].[Na+].O>C(#N)C.C(Cl)Cl.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[CH2:11][CH:12]1[C:23]2[CH:22]=[C:21]([O:24][CH3:25])[C:20]([O:26][CH3:27])=[CH:19][C:18]=2[CH2:17][CH2:16][CH2:15][NH:14]1

Participants

7

Reactant 4

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 4311764Sodium borohydrideHCID 122679872-(3,4-Dimethoxy-phenyl)-N-[3-(3,4-dimethoxy-phenyl)-propyl]-acetamide

Product 1

HCID 122679961-(3,4-Dimethoxy-benzyl)-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-benzo[c]azepine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-(3,4-dimethoxy-phenyl)-N-[3-(3,4-dimethoxy-phenyl)-propyl]-acetamide (6.16 g, 16.5 mmol) and POCl3 (4.95 mL, 54.1 mmol) in anhydrous acetonitrile (185 mL) is stirred at reflux for 4 h under nitrogen. After cooling, the reaction mixture is evaporated and the residue is dissolved in MeOH (125 mL). The solution is cooled to 0° C. and NaBH4 (4.31 g, 114 mmol) is added portionwise. After stirring at 0° C. for 2 h under nitrogen, the reaction mixture is poured into H2O and extracted three times with CH2Cl2. The combined organic extracts are washed with brine, dried over anhydrous MgSO4, filtered and concentrated to give a crude oil. Flash chromatography (CH2Cl2/MeOH: 9/1) yields the title compound as a yellow oil.

Workup

  1. temperatureat reflux for 4 h under nitrogen
  2. temperatureAfter cooling
  3. customthe reaction mixture is evaporated
  4. dissolutionthe residue is dissolved in MeOH (125 mL)
  5. stirringAfter stirring at 0° C. for 2 h under nitrogen
  6. extractionextracted three times with CH2Cl2
  7. washThe combined organic extracts are washed with brine
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a crude oil

Sources & evidence

ORD record
ord-f5d1f5cc2a2841fbaef7f9746b13e242
Source dataset
uspto-grants-2004_11
Patent number
US06815451B2

Reaction notes

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