Triethylamine → Methyl 1-[2-{3-[4-(1,1'-biphenyl-4-ylmethoxy)phenyl]propoxy}-5-(ethoxycarbonyl)-benzoyl]-4-piperidinecarboxylate

HRID 1782769Notes

Reaction equation

HRID 1782769 reaction equation
O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[C:19]1([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH:24]=[CH:23][C:22]([CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][CH2:35][O:36][C:37]3[CH:45]=[CH:44][C:43]([C:46]([O:48][CH2:49][CH3:50])=[O:47])=[CH:42][C:38]=3[C:39]([OH:41])=O)=[CH:29][CH:28]=2)=[CH:21][CH:20]=1.Cl.[NH:58]1[CH2:63][CH2:62][CH:61]([C:64]([O:66][CH3:67])=[O:65])[CH2:60][CH2:59]1>ClCCl.O>[C:19]1([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:24]=[CH:23][C:22]([CH2:25][O:26][C:27]2[CH:28]=[CH:29][C:30]([CH2:33][CH2:34][CH2:35][O:36][C:37]3[CH:45]=[CH:44][C:43]([C:46]([O:48][CH2:49][CH3:50])=[O:47])=[CH:42][C:38]=3[C:39]([N:58]3[CH2:63][CH2:62][CH:61]([C:64]([O:66][CH3:67])=[O:65])[CH2:60][CH2:59]3)=[O:41])=[CH:31][CH:32]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 187838294-Piperidinecarboxylic acid, methyl ester, hydrochloride (1:1)HCID 57589042HCID 57589042, compound

Product 1

HCID 57589096Methyl 1-[2-{3-[4-(1,1'-biphenyl-4-ylmethoxy)phenyl]propoxy}-5-(ethoxycarbonyl)-benzoyl]-4-piperidinecarboxylateYield 96.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

75 mg of N-[(3-dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (EDC), 27 mg of 1-hydroxy-1H-benzotriazole hydrate (HOBT) and 40 mg of triethylamine, are successively added to a suspension of 100 mg of 2-{3-[4-(1,1′-biphenyl-4-ylmethoxy)phenyl]propoxy}-5-(ethoxycarbonyl)benzoic acid and 39 mg of methyl piperidine-4-carboxylate hydrochloride in 30 ml of dichloromethane. Water is added to the reaction mixture after 15 hours at room temperature. After phase separation, the aqueous phase is extracted with ethyl acetate. The combined dichloromethane and ethyl acetate phases are washed with saturated brine and dried over anhydrous sodium sulphate. Filtration and concentration result in a crude product which is purified by suction filtration through silica gel with cyclohexane/ethyl acetate 1:1 as mobile phase. 120 mg of product are obtained.

Workup

  1. customAfter phase separation
  2. extractionthe aqueous phase is extracted with ethyl acetate
  3. washThe combined dichloromethane and ethyl acetate phases are washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationFiltration and concentration
  6. customresult in a crude product which
  7. filtrationis purified by suction filtration through silica gel with cyclohexane/ethyl acetate 1:1 as mobile phase

Sources & evidence

ORD record
ord-d2b43d784765443f96e992ce4337d8c8
Source dataset
uspto-grants-2009_03
Patent number
US07498460B2

Reaction notes

Loading…