4-Fluoro-1-naphthoic acid → 4-fluoro-N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((3-(trifluoromethyl)phenyl)methyl)ethyl)-1-naphthalenecarboxamide

HRID 1610273노트

반응식

HRID 1610273 반응식
[NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[F:23][C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([C:34](O)=[O:35])=[CH:26][CH:25]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[F:23][C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([C:34]([NH:1][CH:2]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:20])[F:21])[CH:14]=2)[CH:3]([C:5]2[CH:6]=[CH:7][C:8]([F:11])=[CH:9][CH:10]=2)[OH:4])=[O:35])=[CH:26][CH:25]=1

참가 물질

7

반응물 4

HCID 684484-Fluoro-1-naphthoic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22261995(1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(3-(trifluoromethyl)phenyl)-1-propanol

생성물 1

HCID 222615784-fluoro-N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((3-(trifluoromethyl)phenyl)methyl)ethyl)-1-naphthalenecarboxamide수율 70.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

실험 절차

To a solution of (1RS,2SR)-2-amino-1-(4-fluorophenyl)-3-(3-(trifluoromethyl)phenyl)-1-propanol (450 mg, 1.44 mmol) in acetonitrile (30 ml) were added 4-fluoronaphthalenecarboxylic acid (274 mg, 1.44 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (358 mg, 1.87 mmol) and 1-hydroxy-1H-benzotriazole (220 mg, 1.44 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 with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). Recrystallization from ethyl acetate-hexane gave the title compound (490 mg, 70%).

후처리

  1. extractionextracted with ethyl acetate (100 ml×2)
  2. washThe extract was washed with 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 (ethyl acetate)
  6. customRecrystallization from ethyl acetate-hexane

출처 및 근거

ORD 기록
ord-4470368843e147f9834fa9bd63caebc3
출처 데이터셋
uspto-grants-2006_01
특허 번호
US06982348B2

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