5-Chloro-1-naphthoic acid → N-[(1RS,2SR)-1-(4-tert-butylbenzyl)-2-(3-chlorophenyl)-2-hydroxyethyl]-5-chloro-1-naphthamide

HRID 1610629Notes

Reaction equation

HRID 1610629 reaction equation
[NH2:1][CH:2]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=1)[CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=1)[OH:4].[Cl:23][C:24]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:25]=1[CH:26]=[CH:27][CH:28]=[C:29]2[C:34](O)=[O:35].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[C:19]([C:16]1[CH:15]=[CH:14][C:13]([CH2:12][CH:2]([NH:1][C:34]([C:29]2[C:30]3[C:25](=[C:24]([Cl:23])[CH:33]=[CH:32][CH:31]=3)[CH:26]=[CH:27][CH:28]=2)=[O:35])[CH:3]([C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[CH:6]=2)[OH:4])=[CH:18][CH:17]=1)([CH3:22])([CH3:21])[CH3:20]

Participants

7

Reactant 4

HCID 9370575-Chloro-1-naphthoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22261970(1RS,2SR)-2-amino-3-(4-tert-butylphenyl)-1-(3-chlorophenyl)propan-1-ol

Product 1

HCID 22262327N-[(1RS,2SR)-1-(4-tert-butylbenzyl)-2-(3-chlorophenyl)-2-hydroxyethyl]-5-chloro-1-naphthamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of (1RS,2SR)-2-amino-3-(4-tert-butylphenyl)-1-(3-chlorophenyl)propan-1-ol (1.0 g, 3.15 mmol) in acetonitrile (40 ml) were added 5-chloronaphthalenecarboxylic acid (651 mg, 3.15 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (725 mg, 3.78 mmol) and 1-hydroxybenzotriazole hydrate (482 mg, 3.15 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (200 ml), and the mixture was extracted with ethyl acetate (200 ml×2). The extract was washed successively with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-1:1). Recrystallization from ethyl acetate-hexane gave the objective substance (1.04 g, 66%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate (200 ml×2)
  2. washThe extract was washed successively with water and saturated brine
  3. dry with materialdried (anhydrous magnesium sulfate)
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1-1:1)
  6. customRecrystallization from ethyl acetate-hexane
  7. customgave the objective substance (1.04 g, 66%)

Sources & evidence

ORD record
ord-13c2814ca7f9434bbeda66598ba33fd4
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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