6-Bromonicotinic acid → HCID 58484616, compound
Reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[CH:11]1([C:14]2[CH:26]=[CH:25][C:17]([O:18][CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[CH:16][CH:15]=2)[CH2:13][CH2:12]1>>[Br:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([N:22]2[CH2:23][CH2:24][CH:19]([O:18][C:17]3[CH:16]=[CH:15][C:14]([CH:11]4[CH2:13][CH2:12]4)=[CH:26][CH:25]=3)[CH2:20][CH2:21]2)=[O:8])=[CH:9][CH:10]=1Participants
Procedure
To a solution of 1-Boc-4-(4-bromophenoxy)piperidine (5 g) in toluene (70 mL) were added dichlorobis(tricyclohexylphosphine)palladium (II) (725 mg), tripotassium phosphate (14.9 g) and cyclopropylboronic acid (1.81 g), and the mixture was refluxed for 7 hr. After cooling, water was added, insoluble materials were filtered off, and the mixture was extracted with ethyl acetate and washed with saturated brine. The solvent was evaporated and the residue was purified by column chromatography to give 4-(4-cyclopropylphenoxy)piperidine-1-carboxylic acid tert-butyl ester. 4-(4-Cyclopropylphenoxy)piperidine-1-carboxylic acid tert-butyl ester was dissolve in ethyl acetate (3 mL), 4N hydrogen chloride/ethyl acetate (7 mL) was added, and the mixture was stirred at room temperature overnight. Water was added, and the mixture was washed with ethyl acetate. To the aqueous solution was added 1N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated to give 4-(4-cyclopropylphenoxy)piperidine (2.49 g). By reaction and treatment in the same manner as in Preparation Example 60 and using 6-bromonicotinic acid (1.2 g) and 4-(4-cyclopropylphenoxy)piperidine (1.4 g), the title compound (2.4 g) was obtained.
Workup
- customBy reaction and treatment in the same manner
- customas in Preparation Example 60
Sources & evidence
- ORD record
- ord-23d10344dfb94fbebebbfd196dba6bd3
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08354401B2
Reaction notes
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