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

HRID 586991Notes

Reaction equation

HRID 586991 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][CH2:39][CH3:40])=[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>[CH2:37]([O:36][CH2:35][CH2:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH2:12][C:13]4[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=4)[CH2:10][CH2:9][C:8]([C:21]([OH:23])=[O:22])=[CH:7][C:6]=3[CH:24]=2)=[CH:32][CH:31]=1)[CH2:38][CH2:39][CH3:40]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 223291907-Bromo-1-(4-methoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylic acidHCID 867568154-Butoxyethoxyphenyl borate

Product 1

HCID 697498537-(4-Butoxyethoxyphenyl)-1-(4-methoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylic acidYield 38.4%

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-butoxyethoxyphenyl borate (368 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 6 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 twice. 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=2:1) and the resulting solid was washed with hexane to give 7-(4-butoxyethoxyphenyl)-1-(4-methoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (149 mg) as yellow crystals.

Workup

  1. temperatureto cool
  2. extractionextracted with ethyl acetate twice
  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=2:1)
  7. washthe resulting solid was washed with hexane

Sources & evidence

ORD record
ord-0590c9e8e69147db81ed7f7240a9f6fe
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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