Ethyl Acetate → Methyl 4-{[{2-[(4'-chloro[1,1'-biphenyl]-4-yl)methoxy]phenethyl}(5-ethoxy-5-oxopentyl)amino]methyl}benzoate

HRID 505615Notes

Reaction equation

HRID 505615 reaction equation
Br[C:2]1[CH:38]=[CH:37][C:5]([CH2:6][O:7][C:8]2[CH:36]=[CH:35][CH:34]=[CH:33][C:9]=2[CH2:10][CH2:11][N:12]([CH2:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=2)[CH2:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:4][CH:3]=1.[Cl:39][C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][CH:41]=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>C(COC)OC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:39][C:40]1[CH:45]=[CH:44][C:43]([C:2]2[CH:3]=[CH:4][C:5]([CH2:6][O:7][C:8]3[CH:36]=[CH:35][CH:34]=[CH:33][C:9]=3[CH2:10][CH2:11][N:12]([CH2:22][C:23]3[CH:24]=[CH:25][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:31][CH:32]=3)[CH2:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:37][CH:38]=2)=[CH:42][CH:41]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 22015004Methyl 4-{[{2-[(4-bromobenzyl)oxy]phenethyl}(5-ethoxy-5-oxopentyl)amino]methyl}benzoate

Product 1

HCID 22015030Methyl 4-{[{2-[(4'-chloro[1,1'-biphenyl]-4-yl)methoxy]phenethyl}(5-ethoxy-5-oxopentyl)amino]methyl}benzoate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

300.0 mg (0.51 mmol) of methyl 4-{[{2-[(4-bromobenzyl)oxy]phenethyl}(5-ethoxy-5-oxopentyl)amino]methyl}benzoate from Ex. 4 are initially charged in 3 ml of dimethoxyethane and admixed successively with 101.7 mg (0.62 mmol) of 4-chlorophenylboronic acid and 0.57 ml of 2M sodium carbonate solution. 10.0 mg of dichlorobis(triphenylphosphine)palladium(II) are added, and the mixture is then heated at reflux temperature for 18 hours. The reaction solution is cooled, admixed with 20 ml of ethyl acetate and washed successively with 5% strength sodium hydrogen phosphate solution, water and saturated sodium chloride solution. The organic phase is dried over magnesium sulphate and the solvent is distilled off under reduced pressure. The crude product is chromatographed over silica gel using the mobile phase cyclohexane/ethyl acetate=10:1.

Workup

  1. temperaturethe mixture is then heated
  2. temperatureat reflux temperature for 18 hours
  3. temperatureThe reaction solution is cooled
  4. washwashed successively with 5% strength sodium hydrogen phosphate solution, water and saturated sodium chloride solution
  5. dry with materialThe organic phase is dried over magnesium sulphate
  6. distillationthe solvent is distilled off under reduced pressure
  7. customThe crude product is chromatographed over silica gel using the mobile phase cyclohexane/ethyl acetate=10:1

Sources & evidence

ORD record
ord-9ec2ddf7bd9541cdb258b8d4f4c98e05
Source dataset
uspto-grants-2010_08
Patent number
US07781470B2

Reaction notes

Loading…