Cesium carbonate → 1'-Butyl-3'-chloro-4-hydroxymethyl-4-phenyl-3,4,5,6-tetrahydro-2H,1'H-[1,4]bipyridinyl-2'-one

HRID 516634

Reaction equation

HRID 516634 reaction equation
[OH:1][CH2:2][C:3]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[CH2:63]([N:67]1[CH:72]=[CH:71][C:70](OS(C(F)(F)F)(=O)=O)=[C:69]([Cl:81])[C:68]1=[O:82])[CH2:64][CH2:65][CH3:66]>FC(C1C=CC=CC=1)(F)F.C(Cl)Cl.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:63]([N:67]1[CH:72]=[CH:71][C:70]([N:6]2[CH2:5][CH2:4][C:3]([CH2:2][OH:1])([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH2:8][CH2:7]2)=[C:69]([Cl:81])[C:68]1=[O:82])[CH2:64][CH2:65][CH3:66]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 778964-Phenylpiperidine-4-methanolHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 25221428Trifluoromethanesulfonic acid 1-butyl-3-chloro-2-oxo-1,2-dihydropyridin-4-yl ester

Product 1

HCID 594970811'-Butyl-3'-chloro-4-hydroxymethyl-4-phenyl-3,4,5,6-tetrahydro-2H,1'H-[1,4]bipyridinyl-2'-one

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 7368(Trifluoromethyl)benzeneSolvent

Conditions

Temperature
100 °C

Procedure

4-Hydroxymethyl-4-phenylpiperidine (0.172 g, 0.9 mmol), palladium(II) acetate (0.007 g, 0.03 mmol), cesium carbonate (0.391 g, 1.2 mmol) and Xantphos (0.035 g, 0.06 mmol) were added to a solution of intermediate D9 (0.2 g, 0.6 mmol) in trifluoromethylbenzene (2 ml). The reaction mixture was heated at 100° C. for 24 hours in a sealed tube, after which it was cooled to room temperature. Subsequently, it was diluted with DCM, H2O (5 ml) and extracted with EtOAc (3×5 ml). The mixture was filtered through diatomaceous earth, and the filtrate was evaporated to dryness. The crude product was purified first by column chromatography (silica gel; eluent: DCM/EtOAc from 90/10 to 0/100) and then by reversed phase HPLC. The desired fractions were collected, evaporated in vacuo and finally freeze dried to yield compound E22 (0.041 g, 18%) as a white foam.

Workup

  1. temperatureafter which it was cooled to room temperature
  2. extractionextracted with EtOAc (3×5 ml)
  3. filtrationThe mixture was filtered through diatomaceous earth
  4. customthe filtrate was evaporated to dryness
  5. customThe crude product was purified first by column chromatography (silica gel; eluent: DCM/EtOAc from 90/10 to 0/100)
  6. customThe desired fractions were collected
  7. customevaporated in vacuo
  8. customfinally freeze dried
  9. customto yield compound E22 (0.041 g, 18%) as a white foam

Sources & evidence

ORD record
ord-b68423f2e2fb4211b3f631f86f3b2c52
Source dataset
uspto-grants-2015_08
Patent number
US09114138B2

Linked notes

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