Water → HCID 67381120, compound

HRID 1804105Notes

Reaction equation

HRID 1804105 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 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

  1. washthe mixture was washed with ethyl acetate
  2. additionTo the aqueous solution 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-14ddd1a5b7ab45fe808336f79159af6c
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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