Potassium Carbonate → (r)-5,11-Dihydro-5-[1-(4-pyrrolidinophenethyl)pyrrolidin-3-yl]dibenzo[b,e][1,4]oxazepine

HRID 2251915Notes

Reaction equation

HRID 2251915 reaction equation
C(=O)([O-])[O-].[K+].[K+].[N:7]1([C:12]2[CH:40]=[CH:39][C:15]([CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][C@@H:20]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4Br)[CH2:19]3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1>[Cu](Br)Br.C1(C)C=CC=CC=1>[N:7]1([C:12]2[CH:40]=[CH:39][C:15]([CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][C@@H:20]([N:23]4[C:33]5[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=5[CH2:31][O:30][C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][C:24]4=5)[CH2:19]3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

5

Reactant 2

HCID 11430Potassium Carbonate2×HCID 69200293(R)-N-[1-(4-Pyrrolidinophenethyl)pyrrolidin-3-yl]-2-(2-bromobenzyloxy)aniline

Product 1

HCID 12990605(r)-5,11-Dihydro-5-[1-(4-pyrrolidinophenethyl)pyrrolidin-3-yl]dibenzo[b,e][1,4]oxazepine

Reagents, catalysts & solvents 2

HCID 24611Copper bromide (CuBr2)Catalyst3×HCID 1140TolueneSolvent2×

Procedure

Potassium carbonate (1.71 g, 12.4 mmol), copper bromide (I) (53 mg, 0.37 mmol) and toluene (30 ml) were added to (R)-N-[1-(4-pyrrolidinophenethyl)pyrrolidin-3-yl]-2-(2-bromobenzyloxy)aniline (1.4 g as mixture). The reaction mixture was heated under reflux for 53 hours and then copper bromide (I) (60 mg, 0.42 mmol) was added thereto. The reaction mixture was heated under reflux for additional 50 hours. Toluene (10 ml), potassium carbonate (1.04 g, 7.52 mmol) and copper bromide (I) (42 mg, 0.29 mmol) were added thereto. The reaction mixture was heated under reflux for 48 hours and then filtered through Celite. Water was added to the filtrate. The organic layer was taken and dried over sodium sulfate. The solvent was evaporated under reduced pressure. A part (187 mg) of the obtained residue (1.12 g) was subjected to the high performance liquid chromatography. After the elution with acetonitrile and water (gradient from 20:80 to 70:30), suitable fractions were collected and distributed into methylene chloride and saturated aqueous sodium hydrogencarbonate solution. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was subjected to the thin layer silica gel chromatography. After the development with hexane and ethyl acetate (1:5), silica gel was collected from proper parts and then eluted with a solvent mixture of methylene chloride and methanol (3:1). The effluents were collected, and he solvent was evaporated under reduced pressure to obtain the title compound in the form of a white solid (25.5mg, yield in 2 steps: 39%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 53 hours
  3. temperatureThe reaction mixture was heated
  4. temperatureunder reflux for additional 50 hours
  5. temperatureThe reaction mixture was heated
  6. temperatureunder reflux for 48 hours
  7. filtrationfiltered through Celite
  8. additionWater was added to the filtrate
  9. dry with materialdried over sodium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. washAfter the elution with acetonitrile and water (gradient from 20:80 to 70:30), suitable fractions
  12. customwere collected
  13. dry with materialThe organic layer was dried over sodium sulfate
  14. customthe solvent was evaporated under reduced pressure
  15. customAfter the development with hexane and ethyl acetate (1:5), silica gel was collected from proper parts
  16. washeluted with a solvent mixture of methylene chloride and methanol (3:1)
  17. customThe effluents were collected
  18. customhe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-fddda20268a944b0b713a27186bdca34
Source dataset
uspto-grants-2008_01
Patent number
US07320973B2

Reaction notes

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