Hydrochloric Acid → methyl 7-(4-propoxyphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate

HRID 586868Notes

Reaction equation

HRID 586868 reaction equation
C(OC([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH3:28])=[CH:21][CH:20]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:29]([O:31][CH3:32])=[O:30])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.[OH-].[Na+].C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[CH2:26]([O:25][C:22]1[CH:21]=[CH:20][C:19]([C:17]2[CH:16]=[CH:15][C:14]3[NH:8][CH2:9][CH2:10][C:11]([C:29]([O:31][CH3:32])=[O:30])=[CH:12][C:13]=3[CH:18]=2)=[CH:24][CH:23]=1)[CH2:27][CH3:28]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 22328959HCID 22328959, compound

Product 1

HCID 22328960methyl 7-(4-propoxyphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

In a mixture of water:ethanol toluene (1:1:10, v/v. 42.0 ml) were dissolved 4-propoxyphenyl borate (746 mg) and methyl 7-bromo-1-(t-butoxycarbonyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1320 mg). To the solution was added potassium carbonate (1145 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (160 mg), and the mixture was heated to reflux under argon atmosphere for 14.5 hours. The mixture was diluted with ethyl acetate, and washed with water and saturated brine, and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (75 g, hexane:ethyl acetate=3:1) to give methyl 1-(t-butoxycarbonyl)-7-(4-propoxyphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate as yellow amorphous. The obtained methyl 1-(t-butoxycarbonyl)-7-(4-propoxyphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate was dissolved in ethyl acetate (80 ml). To the solution was added 6N hydrochloric acid (20 ml) at room temperature, and the mixture was stirred at 100° C. for 30 minutes and neutralized with 1N sodium hydroxide and saturated sodium hydrogen carbonate solution. The separated organic layer was washed with saturated sodium hydrogen carbonate solution, water and saturated brine, and dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crystals, which were washed with ethyl acetate/hexane to give methyl 7-(4-propoxyphenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (947 mg) as yellow crystals. The mother liquor was concentrated, and the residue was purified with silica gel column chromatography (15 g, hexane:ethyl acetate=4:1) to give desired product (147 mg).

Workup

  1. washThe separated organic layer was washed with saturated sodium hydrogen carbonate solution, water and saturated brine
  2. dry with materialdried with anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customto give crystals, which
  5. washwere washed with ethyl acetate/hexane

Sources & evidence

ORD record
ord-ead4650467cf4723af13e30dd9ce6385
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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