1,1-Dibromoethane → Methyl 6-{[7-(2-bromoethoxy)quinolin-4-yl]oxy}-2-methyl-1-benzofuran-3-carboxylate
Reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:26]=[CH:25][C:16]4[C:17]([C:21]([O:23][CH3:24])=[O:22])=[C:18]([CH3:20])[O:19][C:15]=4[CH:14]=3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[Br:33][CH:34](Br)[CH3:35]>CN(C=O)C>[Br:33][CH2:34][CH2:35][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:26]=[CH:25][C:16]4[C:17]([C:21]([O:23][CH3:24])=[O:22])=[C:18]([CH3:20])[O:19][C:15]=4[CH:14]=3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of methyl 6-[(7-hydroxyquinolin-4-yl)oxy]-2-methyl-1-benzofuran-3-carboxylate 121-D (2.4 g, 7.2 mmol) in DMF (20 ml) was added K2CO3 (5 g, 35.8 mmol) a dibromoethane (2.7 g, 14.3 mmol). The reaction mixture was stirred at room temperature overnight. Column chromatography gave methyl 6-{[7-(2-bromoethoxy)quinolin-4-yl]oxy}-2-methyl-1-benzofuran-3-carboxylate 121-E (1.5 g). A solution of compound 121-E (750 mg) and pyrrolidine (351 mg) in DMF (3 ml) was heated to 60° C. for 45 min. The reaction mixture was extracted with EtOAc. Methyl 2-methyl-6-{[7-(2-pyrrolidin-1-ylethoxy)quinolin-4-yl]oxy}benzofuran-3-carboxylate 121-F (110 mg) was purified by silica gel chromatography using 5-10% MeOH/CH2Cl2. Compound 121-F (110 mg) was treated with 20% NaOH (1 ml) in MeOH (1 ml) overnight. The reaction mixture was acidified with AcOH and extracted with EtOAc. The residue was purified by silica gel chromatography using 0-10% MeOH in CH2Cl2 to give 2-methyl-6-{[7-(2-pyrrolidin-1-ylethoxy)quinolin-4-yl]oxy}-1-benzofuran-3-carboxylic acid 121-G (100 mg).
Sources & evidence
- ORD record
- ord-0c24905afc18423fb80738e2df284296
- Source dataset
- uspto-grants-2008_06
- Patent number
- US07381824B2
Reaction notes
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