Morpholine → Tert-butyl 4-((4'-chloro-4-morpholinobiphenyl-2-yl)methyl)piperazine-1-carboxylate

HRID 629601Notes

Reaction equation

HRID 629601 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11](OS(C(F)(F)F)(=O)=O)=[CH:10][C:9]=2[CH2:22][N:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]2)=[CH:4][CH:3]=1.[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[CH:10][C:9]=2[CH2:22][N:23]2[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH2:27][CH2:28]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 87315805Tert-butyl 4-((4'-chloro-4-(trifluoromethylsulfonyloxy)biphenyl-2-yl)methyl)piperazine-1-carboxylate

Product 1

HCID 67227322Tert-butyl 4-((4'-chloro-4-morpholinobiphenyl-2-yl)methyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of EXAMPLE 198B (500 mg), morpholine (80 mg), palladium (II) acetate (22 mg), biphenyl-2-yldi-tert-butylphosphine (50 mg) and cesium carbonate (427 mg) in anhydrous tetrahydrofuran (6 mL) was heated at 50° C. overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic phase was washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated. The crude material was purified by flash column purification with 30-50% ethyl acetate/hexane to afford the title compound.

Workup

  1. washThe organic phase was washed with water, brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by flash column purification with 30-50% ethyl acetate/hexane

Sources & evidence

ORD record
ord-27a84400039948d18e3daaa6438af0ec
Source dataset
uspto-grants-2016_04
Patent number
US09315488B2

Reaction notes

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