tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(2-methylquinolin-5-yl)piperazine-1-carboxylate

HRID 2424403Notes

Reaction equation

HRID 2424403 reaction equation
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.[N:47]1([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1.FC(F)(F)S(O[C:66]1[CH:75]=[CH:74][CH:73]=[C:72]2[C:67]=1[CH:68]=[CH:69][C:70]([CH3:76])=[N:71]2)(=O)=O>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:76][C:70]1[CH:69]=[CH:68][C:67]2[C:72](=[CH:73][CH:74]=[CH:75][C:66]=2[N:50]2[CH2:51][CH2:52][N:47]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:48][CH2:49]2)[N:71]=1

Participants

6

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 498518992-Methylquinolin-5-yl trifluoromethanesulfonate

Product 1

HCID 49851900Tert-butyl 4-(2-methylquinolin-5-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Procedure

A stirred mixture of Pd(OAc)2 (243 mg), CsCO3 (6.63 g), and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.01 g) in dry toluene (60 mL) was heated under reflux for 15 min, under argon. After cooling, a solution of tert-butyl piperazine-1-carboxylate (3.03 g, 16.3 mmol) and the 2-methylquinolin-5-yl trifluoromethane-sulfonate prepared in example 5 (3.95 g, 13.6 mmol) in toluene (100 mL) was added, and the resulting mixture was heated under reflux for 8 h. The reaction mixture was cooled to room temperature, concentrated to half of its value, and then quenched with saturated solution of NH4Cl (50 mL). The organic layer was separated, the aqueous layer was extracted with EtOAc, and the combined organic solutions were concentrated in vacuo. The residue was purified by column chromatography using CH2Cl2 as eluent. Yield: 4.29 g (96.6%), brown oil. Rf=0.64 (CH2Cl2-MeOH (19:1).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 15 min, under argon
  3. temperatureAfter cooling
  4. temperaturethe resulting mixture was heated
  5. temperatureunder reflux for 8 h
  6. concentrationconcentrated to half of its value
  7. customquenched with saturated solution of NH4Cl (50 mL)
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with EtOAc
  10. concentrationthe combined organic solutions were concentrated in vacuo
  11. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-1e89aef938ed41e0bf713e0a0068e51c
Source dataset
uspto-grants-2011_06
Patent number
US07964603B2

Reaction notes

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