Diethyl Ether → tert-Butyl 4-(5-methylpyridin-2-yl)piperazine-1-carboxylate

HRID 2277417Notes

Reaction equation

HRID 2277417 reaction equation
C[C:2]1[CH:7]=[CH:6][C:5](Cl)=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].[CH:22]1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:2]2[CH:7]=[CH:6][C:5]([CH3:22])=[CH:4][N:3]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 27628695-Chloro-2-methylpyridine

Product 1

HCID 45788994tert-Butyl 4-(5-methylpyridin-2-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Under an argon atmosphere, 2.50 g (19.6 mmol) of 2-methyl-5-chloropyridine and 4.38 g (23.5 mmol) of N-(tert-butyloxycarbonyl)-piperazine are dissolved in 50 ml of absolute toluene. Then, 2.26 g (23.5 mmol) of sodium-tert-butylate, 0.37 g (0.59 mmol) of BINAP, and 0.36 g (0.39 mmol) of tris(dibenzylideneacetone)-dipalladium are added, and it is heated for 12 hours to 70° C. After cooling, the reaction mixture is mixed with diethyl ether, washed three times with saturated sodium chloride solution, dried on sodium sulfate, and solvent is removed in a vacuum. The residue is purified by flash chromatography (cyclohexane/ethyl acetate 9:1).

Workup

  1. temperatureit is heated for 12 hours to 70° C
  2. temperatureAfter cooling
  3. washwashed three times with saturated sodium chloride solution
  4. customdried on sodium sulfate, and solvent
  5. customis removed in a vacuum
  6. customThe residue is purified by flash chromatography (cyclohexane/ethyl acetate 9:1)

Sources & evidence

ORD record
ord-eca7c9f093d4463fa5a7b6399bc4194f
Source dataset
uspto-grants-2015_09
Patent number
US09133165B2

Reaction notes

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