Water → HCID 67381120, compound

HRID 2411328Notes

Reaction equation

HRID 2411328 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH:21]3[CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(OCC)(=O)C.O>C(OCC)(=O)C>[CH:21]1([C:18]2[CH:19]=[CH:20][C:15]([O:14][CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[CH:16][CH:17]=2)[CH2:22][CH2:23]1

Participants

5

Reactant 3

HCID 962WaterHCID 21866389Hydrogen chloride-ethyl acetateHCID 67380937HCID 67380937, compound

Product 1

HCID 67381120HCID 67381120, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

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. washthe mixture was washed with ethyl acetate
  2. additionTo the obtained aqueous layer was added 1N aqueous sodium hydroxide solution
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. customthe solvent was evaporated

Sources & evidence

ORD record
ord-9b9b1872967941f09f99a33cc324cb06
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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