Sulfuric Acid → 1-Naphthalenecarboxylic acid, 4-formyl-, methyl ester
Reaction equation
[CH:1](/[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([C:19]([O:21][CH3:22])=[O:20])=[CH:11][CH:10]=1)=C\C1C=CC=CC=1.BrC1C2C(=CC=CC=2)C(C(O)=[O:35])=CC=1.S(=O)(=O)(O)O.C1(/C=C/B(O)O)C=CC=CC=1.C([O-])(O)=O.[Na+]>CCO.C1(C)C=CC=CC=1.[Pd].ClCCl.CO.CO>[CH:1]([C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([C:19]([O:21][CH3:22])=[O:20])=[CH:11][CH:10]=1)=[O:35]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 4
Procedure
In Scheme 1, intermediate (2), (E)-methyl 4-styryl-1-naphthoate can be prepared by reacting commercially available 4-bromo naphthoic acid (1, Combi Blocks, San Diego, Calif.) with methanol in the presence of catalytic sulfuric acid followed by coupling with trans-2-phenylvinyl-boronic acid in EtOH/toluene with a palladium source (e.g., Pd(dppf2)Cl2) and an inorganic base such as NaHCO3. Ozonolysis can be performed on intermediate 2 in a solvent system such as dichloromethane/MeOH to provide the aldehyde 3, methyl 4-formyl-1-naphthoate. The oxime, (E/Z)-methyl 4-((hydroxyimino)methyl)-1-naphthoate (4) can be synthesized by reacting hydroxylamine hydrochloric acid with the precursor aldehyde (3) in a protic solvent such as ethanol (EtOH). The oxime is converted to the isoxazoline in a two step, one reaction pot procedure. Conversion of the oxime to the chloro-oxime with N-chlorosuccinamide in DMF and subsequent cyclization with the aryl olefin 5 (as shown below in Scheme 3A/3B) affords the desired isoxazoline intermediate 6 compounds. Saponification of the intermediate 6 compounds using a base such as LiOH or NaOH in a solvent system such as dioxane/water can be used to afford the naphthoic acid compounds (7) after acidic work-up.
Sources & evidence
- ORD record
- ord-4f85d2e74bb7460889f2854c3b990ce5
- Source dataset
- uspto-grants-2013_03
- Patent number
- US08404649B2
Reaction notes
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