Water → HCID 22328998, compound

HRID 587055Notes

Reaction equation

HRID 587055 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH:12]([CH3:14])[CH3:13])[CH2:10][CH2:9][C:8]([C:15]([O:17][CH3:18])=[O:16])=[CH:7][C:6]=2[CH:19]=1.B([O-])([O-])O[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][CH2:34][CH3:35])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1.C(O)C.O.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>[CH2:32]([O:31][CH2:30][CH2:29][O:28][C:25]1[CH:24]=[CH:23][C:22]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH:12]([CH3:14])[CH3:13])[CH2:10][CH2:9][C:8]([C:15]([O:17][CH3:18])=[O:16])=[CH:7][C:6]=3[CH:19]=2)=[CH:27][CH:26]=1)[CH2:33][CH2:34][CH3:35]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 22329311HCID 22329311, compoundHCID 867568154-Butoxyethoxyphenyl borate

Product 1

HCID 22328998HCID 22328998, compoundYield 65.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86587398Ethanol toluene waterSolvent

Procedure

In toluene/ethanol/water (=10/1/1, 20.4 ml) was dissolved methyl 7-bromo-1-isopropyl-2,3-dihydro-1-benzazepine-4-carboxylate (0.50 g). To the solution were added 4-(2-butoxyethoxy)phenyl borate (0.48 g) and potassium carbonate (0.47 g), and the mixture was stirred for 30 minutes under argon atmosphere. To the mixture was added tetrakistriphenylphosphinepalladium (0.10 g), and the mixture was heated to reflux for 14 hours. After cooled to room temperature, the reaction solution was added to water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried with magnesium sulfate. The solvent was removed under reduced pressure, and the resulting residue was purified with silica gel column chromatography (hexane/ethyl acetate=20/1→8/1) to give methyl 7-[4-(2-butoxyethoxy)phenyl]-1-isopropyl-2,3-dihydro-1-benzazepine-4-carboxylate (0.44 g). Methyl 7-[4-(2-butoxyethoxy)phenyl]-1-isopropyl-2,3-dihydro-1-benzazepine-4-carboxylate (0.44 g) was dissolved in THF (8.8 ml)/methanol (8.8 ml). To the solution was added 1N sodium hydroxide (4.4 ml), and the mixture was stirred at 50° C. for 4 hours. After cooled to room temperature, pH was adjusted to approximate. 5 with 1N hydrochloric acid, and the solvent was concentrated to half under reduced pressure. The concentrated material was extracted with ethyl acetate/THF, and the extract was washed with saturated brine and dried with magnesium sulfate. The solvent was removed under reduced pressure, and the resulting residue was washed with hexane/ethyl acetate (12/1) to give 7-[4-(2-butoxyethoxy)phenyl]-1-isopropyl-2,3-dihydro-1-benzazepine-4-carboxylic acid (320 mg).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 14 hours
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried with magnesium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe resulting residue was purified with silica gel column chromatography (hexane/ethyl acetate=20/1→8/1)

Sources & evidence

ORD record
ord-f5c9cdb6da5a4552824f176e3c5d1abf
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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