Cesium carbonate → HCID 178452081, compound

HRID 1778229Notes

Reaction equation

HRID 1778229 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[C:14]([OH:19])[CH:13]=[C:12]3Br)=[CH:4][CH:3]=1.[NH2:28][CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]=[C:14]([OH:19])[CH:13]=[C:12]3[NH:28][CH:29]2[CH2:30][CH2:31][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:33][CH2:34]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 12682914-Amino-1-Boc-piperidineHCID 178515443HCID 178515443, compound

Product 1

HCID 178452081HCID 178452081, compound

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 6-[bis(4-chlorophenyl)methyl]-4-bromoquinolin-2-ol (500 mg, 1.09 mmol, 1.00 equip), tert-butyl 4-aminopiperidine-1-carboxylate (326.8 mg, 1.63 mmol, 1.50 equip), Pd2(dba)3 (99.8 mg, 0.11 mmol, 0.10 equip), dppf (211 mg, 0.38 mmol, 0.35 equip), Cs2CO3 (882.35 mg, 2.71 mmol, 2.50 equip), and 1,4-dioxane (10 mL). The resulting solution was stirred overnight at 100° C. The reaction was then quenched by the addition of water (100 mL). The resulting solution was extracted with ethyl acetate (3×50 mL) and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The filtrate was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (20:1). The resulting residue was recrystallized from ethyl acetate:petroleum ether in the ratio of 1:10 to yield tert-butyl 4-([6-[bis(4-chlorophenyl)methyl]-2-hydroxyquinolin-4-yl]amino)piperidine-1-carboxylate as an off-white solid. (ES, m/z) 578 [M+H]+

Workup

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customThe reaction was then quenched by the addition of water (100 mL)
  4. extractionThe resulting solution was extracted with ethyl acetate (3×50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe solids were filtered out
  7. concentrationThe filtrate was concentrated under vacuum
  8. customThe resulting residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-c14f666c85be43ea8133b91a0a2975a3
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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