Triethylamine → 4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-propyl)-2-piperazinecarboxylic acid ethyl ester

HRID 363310Notes

Reaction equation

HRID 363310 reaction equation
[CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[N:6]([CH2:16][CH2:17][CH2:18]O)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH2:32]([O:34][C:35]([CH:37]1[CH2:42][NH:41][CH2:40][CH2:39][NH:38]1)=[O:36])[CH3:33].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O>[CH2:32]([O:34][C:35]([CH:37]1[CH2:42][N:41]([CH2:18][CH2:17][CH2:16][N:6]2[C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=3[CH2:9][CH2:10][C:11]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]2=3)[CH2:40][CH2:39][NH:38]1)=[O:36])[CH3:33]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 10633257Ethyl Piperazine-2-carboxylateHCID 110214143-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol

Product 1

HCID 543687374-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-propyl)-2-piperazinecarboxylic acid ethyl esterYield 33%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-(10,11 -dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.17 g, 0.0046 mol, prepared similarly as described in example 2) and triethylamine (1.18 g, 0.012 mol) in toluene (30 ml) at 0° C., methanesulfonyl chloride (0.70 ml, 0.009 mol) was added dropwise over 10 minutes. The resulting mixture was stirred at 0° C. for 1 h. Toluene (50 ml) and water (100 ml) were added, and the phases were separated. The aqueous layer was extracted with toluene (50 ml), and the combined organic phases were washed with brine (2×100 ml), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in acetonitrile (10 ml) and the above 2-piperazine-carboxylic acid ethyl ester (1.40 g, 0.0089 mol), potassium carbonate (0.67 g, 0.0049 mol) and toluene (5 ml) were added. The resulting mixture was heated at reflux temperature for 18 h. Water (50 ml) was added, and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (27 g) using a gradient of methanol and ethyl acetate (5:100→20:100), affording 0.6 g (33%) of 4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-2-piperazinecarboxylic acid ethyl ester as an oil.

Workup

  1. customat 0° C.
  2. customthe phases were separated
  3. extractionThe aqueous layer was extracted with toluene (50 ml)
  4. washthe combined organic phases were washed with brine (2×100 ml)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in acetonitrile (10 ml)
  8. temperatureThe resulting mixture was heated
  9. temperatureat reflux temperature for 18 h
  10. extractionthe mixture was extracted with ethyl acetate (3×20 ml)
  11. washThe combined organic extracts were washed with brine (2×20 ml)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified by column chromatography on silica gel (27 g)

Sources & evidence

ORD record
ord-fa803c4342124651b151e7aee95ee106
Source dataset
uspto-grants-1999_02
Patent number
US05874428

Reaction notes

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