Toluene → 4-(3-Chloro-5-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester

HRID 2411213Notes

Reaction equation

HRID 2411213 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl[C:15]1[C:20]([Cl:21])=[CH:19][C:18]([CH3:22])=[CH:17][N:16]=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][N:11]([C:15]2[C:20]([Cl:21])=[CH:19][C:18]([CH3:22])=[CH:17][N:16]=2)[CH2:12][CH2:13]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

8

Reactant 4

HCID 1140TolueneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 127477612,3-Dichloro-5-methylpyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 673809194-(3-Chloro-5-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl esterYield 93.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolvent

Procedure

To a mixture of 1-Boc-piperazine (7.2 g), 2,3-dichloro-5-methylpyridine (5 g), palladium(II) acetate (179 mg), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (499 mg) and sodium tert-butoxide (4.1 g) was added toluene (30 mL), and the mixture was stirred with heating under reflux for 5 hr. The reaction mixture was cooled, water was added, and the mixture 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 (hexane:ethyl acetate) to give 4-(3-chloro-5-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (9 g). To a mixture of the obtained 4-(3-chloro-5-methylpyridin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (9 g),

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 5 hr
  3. temperatureThe reaction mixture was cooled
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. customthe solvent was evaporated
  7. customThe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-94abbb70a1bc48ec81a0a0daf70c8f91
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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