Cesium carbonate → Tert-butyl 4-(4-(2-methoxy-2-oxoethyl)phenyl)piperazine-1-carboxylate

HRID 2229148Notes

Reaction equation

HRID 2229148 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.FC(F)(F)S(O[C:59]1[CH:64]=[CH:63][C:62]([CH2:65][C:66]([O:68][CH3:69])=[O:67])=[CH:61][CH:60]=1)(=O)=O.[C:72]([O:76][C:77]([N:79]1[CH2:84][CH2:83][NH:82][CH2:81][CH2:80]1)=[O:78])([CH3:75])([CH3:74])[CH3:73]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:72]([O:76][C:77]([N:79]1[CH2:84][CH2:83][N:82]([C:59]2[CH:64]=[CH:63][C:62]([CH2:65][C:66]([O:68][CH3:69])=[O:67])=[CH:61][CH:60]=2)[CH2:81][CH2:80]1)=[O:78])([CH3:75])([CH3:73])[CH3:74]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 10542066Methyl 2-{4-[(trifluoromethyl)sulfonyloxy]phenyl}acetate

Product 1

HCID 18466559Tert-butyl 4-(4-(2-methoxy-2-oxoethyl)phenyl)piperazine-1-carboxylateYield 50.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A flask charged with cesium carbonate (4.6 g, 14.0 mmol), palladium (II) acetate (0.07 g, 0.3 mmol), and (S)-BINAP (0.28 g, 4.5 mmol) was evacuated and flushed with dry nitrogen. Methyl 2-{4-[(trifluoromethyl)sulfonyloxy]phenyl}acetate (3.0 g, 10.0 mmol) and t-butyl-1-piperazinecarboxylate (2.3 g, 12.0 mmol) in 20 mL toluene was added via syringe and the resultant mixture was stirred at ambient temperature for 30 minutes and at 80° C. for 16 hours. The reaction mixture was removed from the heating bath, concentrated, and chromatographed on silica gel (0 to 30% ethyl acetate/hexane) providing 1.7 g (50%) of the title compound. 1H NMR (300 MHz, CDCl3) δ7.20 (d, J=8.5 Hz, 2H), 6.89 (d, J=8.4 Hz, 2H), 3.70 (s, 3H), 3.59 (t, J=5.0 Hz, 4H), 3.57 (s, 2H), 3.12 (t, J=5.2 Hz, 4H), 1.50 (s, 9H); ESI (M+H)+=335.

Workup

  1. customwas evacuated
  2. customflushed with dry nitrogen
  3. customThe reaction mixture was removed from the heating bath
  4. concentrationconcentrated
  5. customchromatographed on silica gel (0 to 30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-31a4b7e45d7840b6b9ae73b24988fb7d
Source dataset
uspto-grants-2002_07
Patent number
US06420349B1

Reaction notes

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