Hydrochloric Acid → 1-(4-Methoxybenzyl)-7-(4-propoxyethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid

HRID 586990Notes

Reaction equation

HRID 586990 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[CH2:10][CH2:9][C:8]([C:21]([OH:23])=[O:22])=[CH:7][C:6]=2[CH:24]=1.B([O-])([O-])O[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][CH3:39])=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].Cl>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([CH2:12][N:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:27]4[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][CH3:39])=[CH:29][CH:28]=4)=[CH:24][C:6]=3[CH:7]=[C:8]([C:21]([OH:23])=[O:22])[CH2:9][CH2:10]2)=[CH:14][CH:15]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 223291907-Bromo-1-(4-methoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylic acidHCID 867568144-(2-Propoxyethoxy)phenyl borate

Product 1

HCID 697500961-(4-Methoxybenzyl)-7-(4-propoxyethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxylic acidYield 31.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In toluene (20 ml), ethanol (2 ml) and water (2 ml) were suspended 7-bromo-1-(4-methoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (300 mg), 4-propoxyethoxyphenyl borate (346 mg) and potassium carbonate (534 mg), and the suspension was stirred under argon atmosphere for 30 minutes. Then, to the suspension was added tetrakistriphenylphosphinepalladium (63 mg), and the mixture was heated at 100° C. for 4 hours under argon atmosphere. After allowing to cool, water was added to the mixture, which was made acidic (pH=4) with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, the resulting residue was purified with silica gel column chromatography (hexane:ethyl acetate=1:1) and the resulting solid was recrystallized from hexane-ethyl acetate to give 1-(4-methoxybenzyl)-7-(4-propoxyethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (117 mg) as yellow crystals.

Workup

  1. temperatureto cool
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine
  4. dry with materialdried with magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe resulting residue was purified with silica gel column chromatography (hexane:ethyl acetate=1:1)
  7. customthe resulting solid was recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-1ee8ff789f0a46129d17c949b88ca96b
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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