Cesium carbonate → Tert-butyl 4-(6-(methoxycarbonyl)pyridin-3-yl)piperazine-1-carboxylate

HRID 711256Notes

Reaction equation

HRID 711256 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1.[N:12]1([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C1C=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([O-])([O-])=O.[Cs+].[Cs+]>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].C1(C)C=CC=CC=1>[CH3:11][O:10][C:8]([C:5]1[N:6]=[CH:7][C:2]([N:15]2[CH2:14][CH2:13][N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:17][CH2:16]2)=[CH:3][CH:4]=1)=[O:9]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 7016458Methyl 5-bromopyridine-2-carboxylate

Product 1

HCID 86679721Tert-butyl 4-(6-(methoxycarbonyl)pyridin-3-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a flask containing methyl 5-bromopicolinate 49-1 (1.48 g, 6.85 mmol), tert-butyl piperazine-1-carboxylate 49-2 (1.53 g, 8.22 mmol), Pd2(dba)3 (315 mg, 0.34 mmol), BINAP (462 mg, 0.69 mmol) and Cs2CO3 (5.50 g, 17.20 mmol) under argon was added anhydrous toluene (30 mL). The mixture was stirred at 100° C. for 10 hours. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was redissolved in ethyl acetate (100 mL), washed with H2O and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography, eluted with 5% methanol in dichloromethane to give tert-butyl 4-(6-(methoxycarbonyl)pyridin-3-yl)piperazine-1-carboxylate 49-3 as a yellow solid. MS m/z 322.1 (M+1)

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed by rotary evaporation
  3. dissolutionThe residue was redissolved in ethyl acetate (100 mL)
  4. washwashed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness by rotary evaporation
  7. customThe crude product was purified by silica gel flash chromatography
  8. washeluted with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-71b3e10b33684a4ab84833459d9fa416
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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