Water → Methyl 1-amino-4-(4-chlorobenzyl)-2-naphthoate
Reaction equation
Br.[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](Br)=[CH:5][C:4]=1[C:14]([O:16][CH3:17])=[O:15].[Cl-].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][Zn+])=[CH:22]N=1.O.Cl[CH2:30]Cl>C1COCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[NH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:26][C:23]2[CH:22]=[CH:30][C:20]([Cl:19])=[CH:25][CH:24]=2)=[CH:5][C:4]=1[C:14]([O:16][CH3:17])=[O:15]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of methyl 1-amino-4-bromo-2-naphthoate hydrobromide (1.94 g, 5.37 mmol) in 10 mL of THF at 0° C. under an atmosphere of nitrogen was added (2-chloro-5-pyridyl)methylzinc chloride (41.6 mL, 0.5 M in THF, 83.2 mmol) and bis(tri-tert-butylphosphine)palladium(0) (0.177 g, 0.346 mmol). The reaction was warmed to rt, and after 16 h, treated with water (10 mL). The mixture was diluted dichloromethane and water, and a beige solid was removed via filtration. The filtrate was extracted 2× with dichloromethane and the combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-20% ethyl acetate in hexanes provide methyl 1-amino-4-(4-chlorobenzyl)-2-naphthoate that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 326.1 for [M+H]+.
Workup
- customa beige solid was removed via filtration
- extractionThe filtrate was extracted 2× with dichloromethane
- dry with materialthe combined organic fractions were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified via silica gel chromatography
- washeluting with 0-20% ethyl acetate in hexanes
Sources & evidence
- ORD record
- ord-286af83c7eae4a06b3c0512b878b29de
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08846702B2
Reaction notes
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