Cesium carbonate → Tert-butyl 4-(4-(4-(ethoxycarbonyl)oxazol-5-yl)phenyl)piperazine-1-carboxylate

HRID 714963Notes

Reaction equation

HRID 714963 reaction equation
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:44]1[CH:49]=[CH:48][C:47]([C:50]2[O:54][CH:53]=[N:52][C:51]=2[C:55]([O:57][CH2:58][CH3:59])=[O:56])=[CH:46][CH:45]=1.[N:60]1([C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(O)(C)(C)C.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]>[CH2:58]([O:57][C:55]([C:51]1[N:52]=[CH:53][O:54][C:50]=1[C:47]1[CH:48]=[CH:49][C:44]([N:63]2[CH2:62][CH2:61][N:60]([C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])[CH2:65][CH2:64]2)=[CH:45][CH:46]=1)=[O:56])[CH3:59]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2758809Ethyl 5-(4-bromophenyl)oxazole-4-carboxylate

Product 1

HCID 59587530Tert-butyl 4-(4-(4-(ethoxycarbonyl)oxazol-5-yl)phenyl)piperazine-1-carboxylateYield 50.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tris(dibenzylideneacetone)dipalladium(0) (0.079 g, 0.09 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.100 g, 0.17 mmol), ethyl 5-(4-bromophenyl)oxazole-4-carboxylate (0.500 g, 1.69 mmol), tert-butyl 1-piperazinecarboxylate (0.409 g, 2.20 mmol) and cesium carbonate (0.786 g, 2.41 mmol) in dioxane (25 ml) and t-butanol (25 ml) was degassed, placed under a nitrogen atmosphere and heated under reflux overnight. The solvent was removed in vacuo and the residue partitioned between water and DCM. The organic phase was dried over MgSO4 and the solvent removed in vacuo. The residue was purified by silica gel column chromatography using 50% EtOAc in hexane as eluant to afford tert-butyl 4-(4-(4-(ethoxycarbonyl)oxazol-5-yl)phenyl)piperazine-1-carboxylate (0.340 g, 0.85 mmol, 50%) of a yellow solid. 1H NMR (CDCl3) δ 1.42 (3H, t), 1.49 (9H, s), 3.28 (4H, br. t), 3.59 (4H, br. t), 4.42 (2H, q), 6.95 (2H, d), 7.83 (1H, s), 8.05 (2H, d). LCMS (1) Rt: 2.37 min; m/z (ES+) 402.

Workup

  1. temperatureheated
  2. temperatureunder reflux overnight
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between water and DCM
  5. dry with materialThe organic phase was dried over MgSO4
  6. customthe solvent removed in vacuo
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-990f5824730e400e85d1f5cfe7a14c4d
Source dataset
uspto-grants-2015_11
Patent number
US09187465B2

Reaction notes

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