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

HRID 413681Notes

Reaction equation

HRID 413681 reaction equation
Cl.[CH:2]1[C:12]2[C:11]3[CH2:13][CH2:14][CH:15]=[CH:16][C:10]=3[CH:9]=[CH:8][N:7]([CH2:17][CH:18]([OH:35])[CH2:19][N:20]3[CH2:25][CH2:24]N(C4N=CC=CC=4C(O)=O)C[CH2:21]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:36]([O:38][C:39]([CH:41]1CCNC[CH2:42]1)=[O:40])[CH3:37]>CC(=O)CC>[CH2:36]([O:38][C:39]([CH:41]1[CH2:42][CH2:21][N:20]([CH2:19][CH:18]([OH:35])[CH2:17][N:7]2[C:6]3[CH:5]=[CH:4][CH:3]=[CH:2][C:12]=3[CH2:11][CH2:13][C:14]3[CH:15]=[CH:16][CH:10]=[CH:9][C:8]2=3)[CH2:25][CH2:24]1)=[O:40])[CH3:37]

Participants

4

Reactant 2

HCID 70770Ethyl 4-piperidinecarboxylateHCID 700114662-(4-(3-(10,11-Dihydro-5H-dibenzo[b,d]azepin-5-yl)-2-hydroxypropyl)piperazin-1-yl)nicotinic Acid Hydrochloride

Product 1

HCID 539238781-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxy-propyl)-4-piperidinecarboxylic acid ethyl esterYield 16%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

A mixture of crude (10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2,3-epoxypropane (22.6 g, 90 mmol, prepared as described in Example 19) and 4-piperidinecarboxylic acid ethyl ester (14.15 g, 90 mmol) in dry 2-butanone (50 ml) was stirred and heated at reflux temperature for 24 h. The solvent was removed in vacuo and the residue was dissolved in toluene (250 ml) and water (250 ml). The pH was adjusted to 6 by addition of 1 N hydrochloric acid. The organic phase was separated, washed with water (3×100 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 (20:20:1) as eluent to give 5.8 g (16%) of 1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxy-propyl)-4-piperidinecarboxylic acid ethyl ester as an oil.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature for 24 h
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in toluene (250 ml)
  5. additionThe pH was adjusted to 6 by addition of 1 N hydrochloric acid
  6. customThe organic phase was separated
  7. washwashed with water (3×100 ml)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by column chromatography on silica gel using
  11. additiona mixture of toluene, ethyl acetate and triethylamine (20:20:1) as eluent

Sources & evidence

ORD record
ord-9a6017c3a9824bcc930c768d5983c0ee
Source dataset
uspto-grants-2003_05
Patent number
US06569849B1

Reaction notes

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