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

HRID 586872ノート

反応式

HRID 586872 の反応式
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][CH3:27])=[C:21]([F:28])[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:23]=[CH:24][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:20][C:21]=1[F:28])[CH3:27]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 22329117methyl 1-(t-butoxycarbonyl)-7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate

生成物 1

HCID 22328971methyl 7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate収率 86%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒2 回

実験手順

In a mixture of water:ethanol toluene (1:1:10, v/v, 42.0 ml) were dissolved 4-ethoxy-3-fluorophenyl borate (754 mg) and methyl 7-bromo-1-(t-butoxycarbonyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1305 mg). To the solution was added potassium carbonate (1132 mg), and the mixture was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (158 mg), and the mixture was heated to reflux under argon atmosphere for 10 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=4:1) to give methyl 1-(t-butoxycarbonyl)-7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate as yellow amorphous. The obtained methyl 1-(t-butoxycarbonyl)-7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate was dissolved in ethyl acetate (80 ml). To the solution was added 1N hydrochloric acid (15 ml) at room temperature, and the mixture was stirred at 100° C. for 1 hour and neutralized with 1N sodium hydroxide and saturated sodium hydrogen carbonate solution. To the mixture was added ethyl acetate, and 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, and the residue was purified with silica gel column chromatography (50 g, hexane:ethyl acetate=9:1→4:1→2:1) to give methyl 7-(4-ethoxy-3-fluorophenyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylate (1007 mg, 86%) as yellow crystals.

後処理

  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. customthe residue was purified with silica gel column chromatography (50 g, hexane:ethyl acetate=9:1→4:1→2:1)

出典と根拠

ORDレコード
ord-c6073ae37a7d4236aedc28e28d3e272e
出典データセット
uspto-grants-2005_08
特許番号
US06936602B1

反応ノート

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