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

HRID 413682Notes

Reaction equation

HRID 413682 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]N3CCN(C4N=CC=CC=4C(O)=O)CC3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([C@@H]([C@H](C(O)=O)O)O)(O)=O.[CH2:46]([O:48][C:49]([C@@H:51]1[CH2:56][CH2:55][CH2:54][NH:53][CH2:52]1)=[O:50])[CH3:47].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C)C=O>[CH2:46]([O:48][C:49]([C@@H:51]1[CH2:56][CH2:55][CH2:54][N:53]([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)[CH2:52]1)=[O:50])[CH3:47]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 14183616Ethyl (R)-Nipecotate L-TartrateHCID 700114662-(4-(3-(10,11-Dihydro-5H-dibenzo[b,d]azepin-5-yl)-2-hydroxypropyl)piperazin-1-yl)nicotinic Acid Hydrochloride

Product 1

HCID 70010011(R)-1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxy-propyl)-3-piperidinecarboxylic acid ethyl esterYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of crude (10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2,3-epoxypropane (6.0 g, 20.8 mmol, prepared as described in Example 19), (R)-3-piperidinecarboxylic acid ethyl ester (L)-tartrate (6.24 g, 20.8 mmol), potassium carbonate (11.5 g, 83.2 mmol) and sodium iodide (3.12 g, 20.8 mmol) in dry N,N-dimethylformamide (25 ml) was stirred and heated at 60° C. for 48 h. The reaction mixture was concentrated in vacuo and the residue dissolved in toluene (100 ml) and ethyl acetate (100 ml). The solution was washed with water (2×50 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 4.5 g (53%) of (R)-1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxy-propyl)-3-piperidinecarboxylic acid ethyl ester as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in toluene (100 ml)
  3. washThe solution was washed with water (2×50 ml)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography on silica gel using
  7. additiona mixture of toluene, ethyl acetate and triethylamine (35:6:1) as eluent

Sources & evidence

ORD record
ord-8d59a31d291b434192d30e6af436cb09
Source dataset
uspto-grants-2003_05
Patent number
US06569849B1

Reaction notes

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