1-Bromopropane → 1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-propoxypropyl)-4-piperidinecarboxylic acid ethyl ester

HRID 413684Notes

Reaction equation

HRID 413684 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH:15]([OH:32])[CH2:16][N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[CH2:21][CH2:20][C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]2=3)[CH2:10][CH2:9]1)=[O:7])[CH3:4].[CH2:33](Br)[CH2:34][CH3:35]>CN(C)C=O>[CH2:3]([O:5][C:6]([CH:8]1[CH2:9][CH2:10][N:11]([CH2:14][CH:15]([O:32][CH2:33][CH2:34][CH3:35])[CH2:16][N:17]2[C:18]3[CH:31]=[CH:30][CH:29]=[CH:28][C:19]=3[CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]2=3)[CH2:12][CH2:13]1)=[O:7])[CH3:4]

Participants

5

Reactant 3

HCID 78401-BromopropaneHCID 24758Sodium hydrideHCID 539238781-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxy-propyl)-4-piperidinecarboxylic acid ethyl ester

Product 1

HCID 542754701-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-propoxypropyl)-4-piperidinecarboxylic acid ethyl esterYield 9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% oil suspension, 0.108 g, 2.7 mmol) was added to a stirred solution of 1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxy-propyl)-4-piperidinecarboxylic acid ethyl ester (1.1 g, 2.7 mmol) in dry N,N-dimethylformamide (7.5 ml). Propylbromide (0.7 g, 5.68 mmol) was added dropwise to the ice-cooled stirred solution and the reaction mixture was left at room temperature for 16 h. The mixture was concentrated in vacuo. The residue was dissolved in toluene (20 ml), washed with water (3×10 ml), dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a mixture of toluene, ethyl acetate and triethylamine (35:6:1) as eluent to give 0.11 g (9%) of 1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-propoxypropyl)-4-piperidinecarboxylic acid ethyl ester as an oil.

Workup

  1. temperaturecooled
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in toluene (20 ml)
  4. washwashed with water (3×10 ml)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography on silica gel using
  8. additiona mixture of toluene, ethyl acetate and triethylamine (35:6:1) as eluent

Sources & evidence

ORD record
ord-76b8abc156cc4ee3ad00a99734eca7ae
Source dataset
uspto-grants-2003_05
Patent number
US06569849B1

Reaction notes

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