1-Hydroxybenzotriazole → N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-((methyloxy)methyl)-1-naphthalenecarboxamide

HRID 1610215ノート

反応式

HRID 1610215 の反応式
[NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[CH3:23][O:24][CH2:25][C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]([C:36](O)=[O:37])=[CH:28][CH:27]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:11][C:8]1[CH:9]=[CH:10][C:5]([CH:3]([OH:4])[CH:2]([NH:1][C:36]([C:29]2[C:30]3[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:26]([CH2:25][O:24][CH3:23])=[CH:27][CH:28]=2)=[O:37])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][CH:14]=2)=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 127491544-Methoxymethyl-1-naphthoic acidHCID 22261479(1RS,2RS)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine

生成物 1

HCID 22262228N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-((methyloxy)methyl)-1-naphthalenecarboxamide収率 69.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

実験手順

To a solution of (1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(4-(trifluoromethyl)phenyl)-1-propanol (300 mg, 0.96 mmol) in acetonitrile (30 ml) were added 4-((methyloxy)methyl)-1-naphthalenecarboxylic acid (207 mg, 0.96 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (275 mg, 1.44 mmol) and 1-hydroxy-1H-benzotriazole (147 mg, 0.96 mmol) and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml), and extracted with ethyl acetate (100 ml×2). The extract was washed successively with 1N hydrochloric acid, 1N aqueous sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-2:1) and recrystallized from ethyl acetate-hexane to give the title compound (340 mg, 69%).

後処理

  1. extractionextracted with ethyl acetate (100 ml×2)
  2. washThe extract was washed successively with 1N hydrochloric acid, 1N aqueous sodium hydroxide solution and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-2:1)
  6. customrecrystallized from ethyl acetate-hexane

出典と根拠

ORDレコード
ord-70c91bc593ed43a883d002b23b738342
出典データセット
uspto-grants-2006_01
特許番号
US06982348B2

反応ノート

読み込み中…