Cesium carbonate → 4'-[4-[4-(cis-2,6-Dimethylmorpholin-4-yl)phenyl]piperazin-1-yl]-1,1'-biphenyl-4-carboxylic acid methyl ester

HRID 1816755Notes

Reaction equation

HRID 1816755 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].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.[CH3:53][C@H:54]1[O:59][C@@H:58]([CH3:60])[CH2:57][N:56]([C:61]2[CH:66]=[CH:65][C:64]([N:67]3[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]3)=[CH:63][CH:62]=2)[CH2:55]1.[CH3:73][O:74][C:75]([C:77]1[CH:82]=[CH:81][C:80]([C:83]2[CH:88]=[CH:87][C:86](OS(C(F)(F)F)(=O)=O)=[CH:85][CH:84]=2)=[CH:79][CH:78]=1)=[O:76]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:73][O:74][C:75]([C:77]1[CH:82]=[CH:81][C:80]([C:83]2[CH:88]=[CH:87][C:86]([N:70]3[CH2:69][CH2:68][N:67]([C:64]4[CH:63]=[CH:62][C:61]([N:56]5[CH2:55][C@H:54]([CH3:53])[O:59][C@H:58]([CH3:60])[CH2:57]5)=[CH:66][CH:65]=4)[CH2:72][CH2:71]3)=[CH:85][CH:84]=2)=[CH:79][CH:78]=1)=[O:76]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 22492882Methyl 4'-(trifluoromethanesulfonyloxy)-[1,1'-biphenyl]-4-carboxylateHCID 69677628cis-2,6-Dimethyl-4-(4-piperazinylphenyl)morpholine

Product 1

HCID 538200644'-[4-[4-(cis-2,6-Dimethylmorpholin-4-yl)phenyl]piperazin-1-yl]-1,1'-biphenyl-4-carboxylic acid methyl esterYield 55.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of cesium carbonate (6.33 q), palladium(II) acetate (156 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (648 mg) in dioxane (28 ml) was successively added cis-2,6-dimethyl-4-(4-piperazinylphenyl)morpholine (4.59 g) and 4′-trifluoromethanesulfonyloxy-1,1′-biphenyl-4-carboxylic acid methyl ester (5 g) in a stream of nitrogen. The mixture was stirred at ambient temperature for 30 minutes and at 80° C. for a further 28 hours. After cooling to room temperature, water was added to the reaction mixture. The resulting precipitates were filtered, washed with water and dried to give 4′-[4-[4-(cis-2,6-dimethylmorpholin-4-yl)phenyl]piperazin-1-yl]-1,1′-biphenyl-4-carboxylic acid methyl ester (3.72 g).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe resulting precipitates
  3. filtrationwere filtered
  4. washwashed with water
  5. customdried

Sources & evidence

ORD record
ord-c11f88886d5e44819fc564f510cccb82
Source dataset
uspto-grants-2005_04
Patent number
US06884868B1

Reaction notes

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