6-Bromonicotinic acid → HCID 58484616, compound

HRID 2411329Notes

Reaction equation

HRID 2411329 reaction equation
[CH:1]1([C:4]2[CH:16]=[CH:15][C:7]([O:8][CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.[Br:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][N:19]=1>>[Br:17][C:18]1[N:19]=[CH:20][C:21]([C:22]([N:12]2[CH2:13][CH2:14][CH:9]([O:8][C:7]3[CH:15]=[CH:16][C:4]([CH:1]4[CH2:2][CH2:3]4)=[CH:5][CH:6]=3)[CH2:10][CH2:11]2)=[O:23])=[CH:25][CH:26]=1

Participants

3

Reactant 2

HCID 2389326-Bromonicotinic acidHCID 67381120HCID 67381120, compound

Product 1

HCID 58484616HCID 58484616, compoundYield 100.7%

Procedure

To a mixture of 1-Boc-4-(4-bromophenoxy)piperidine (5 g), dichlorobis(tricyclohexylphosphine)palladium(II) (725 mg), tripotassium phosphate (14.9 g) and cyclopropylboronic acid (1.81 g) was added toluene (70 mL), and the mixture was stirred with heating under reflux for 7 hr. The reaction mixture was cooled, water was added, and the insoluble material was collected by filtration. The filtrate was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography to give 4-(4-cyclopropylphenoxy)piperidine-1-carboxylic acid tert-butyl ester. The obtained 4-(4-cyclopropylphenoxy)piperidine-1-carboxylic acid tert-butyl ester was dissolved 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 to the reaction mixture, and the mixture was washed with ethyl acetate. To the obtained aqueous layer 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). Using the obtained 4-(4-cyclopropylphenoxy)piperidine (1.4 g) and 6-bromonicotinic acid (1.2 g) and by the reaction and treatment in the same manner as in Preparation Example 111, the title compound (2.4 g) was obtained.

Workup

  1. customby the reaction and treatment in the same manner
  2. customas in Preparation Example 111

Sources & evidence

ORD record
ord-3abaa89a21104e10a0d0060155e07288
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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