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

HRID 1610478Notes

Reaction equation

HRID 1610478 reaction equation
[NH2:1][CH:2]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[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]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[CH:3]([OH:4])[C:5]2[CH:10]=[CH:9][C:8]([C:11]([F:12])([F:13])[F:14])=[CH:7][CH:6]=2)=[O:35])=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 684484-Fluoro-1-naphthoic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22261902(1RS,2SR)-2-amino-3-(4-fluorophenyl)-1-(4-(trifluoromethyl)phenyl)-1-propanol

Product 1

HCID 222622464-fluoro-N-((1RS,2SR)-1-((4-fluorophenyl)methyl)-2-hydroxy-2-(4-(trifluoromethyl)phenyl)ethyl)-1-naphthalenecarboxamideYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of (1RS,2SR)-2-amino-3-(4-fluorophenyl)-1-(4-(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 (430 mg, 62%).

Workup

  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

Sources & evidence

ORD record
ord-196082515bfb4bef9a95344639cf0afe
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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