Potassium Iodide → 2-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester

HRID 1166418Notes

Reaction equation

HRID 1166418 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.[CH3:32][O:33][C:34]([CH:36]1[CH2:45][C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][NH:37]1)=[O:35].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>ClCCl.O.CN(C)C=O>[CH3:32][O:33][C:34]([CH:36]1[CH2:45][C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][N:37]1[CH2:18][CH2:17][CH2:16][N:6]1[C:7]2[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=2[CH2:9][CH2:10][C:11]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]1=2)=[O:35]

Participants

10

Reactant 6

HCID 4875Potassium IodideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 4685119Methyl 1,2,3,4-tetrahydroisoquinoline-3-carboxylateHCID 110214143-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol

Product 1

HCID 544781902-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl esterYield 76%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.05 g, 0.0041 mol, prepared similarly as described in example 2) in dichloromethane (40 ml) at 0° C., triethylamine (1.28 g, 0.013 mol) was added, followed by methanesulfonyl chloride (0.9 ml, 0.012 mol). After stirring for 30 minutes at 0° C., water (50 ml) was added and the phases were separated. The organic layer was washed with brine (20 ml), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in acetonitrile (12 ml), and 1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester (1.13 g, 0.0050 mol), N,N-dimethylformamide (5 ml), potassium carbonate (1.32 g, 0.0096 mol) and potassium iodide (0.30 g, 0.0018 mol) were added. The reaction mixture was heated at 82° C. for 12 h. N,N-Dimethylformamide (5 ml) was added and heating was continued for further 16 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 product was purified by column chromatography on silica gel (80 g) using a gradient of heptane and ethyl acetate (10:0→10:3), affording 1.4 g (76%) of 2-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester as an oil.

Workup

  1. customat 0° C.
  2. customthe phases were separated
  3. washThe organic layer was washed with brine (20 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in acetonitrile (12 ml)
  7. temperatureThe reaction mixture was heated at 82° C. for 12 h
  8. temperatureheating
  9. waitwas continued for further 16 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 product was purified by column chromatography on silica gel (80 g)

Sources & evidence

ORD record
ord-6ff8adb7e0dd4fefbf085a988136a304
Source dataset
uspto-grants-2003_09
Patent number
US06613791B1

Reaction notes

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