Potassium Carbonate → HCID 67284990, compound

HRID 1618711Notes

Reaction equation

HRID 1618711 reaction equation
C([O-])([O-])=O.[K+].[K+].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl[C:42]1[C:51]([CH3:52])=[C:50]([Cl:53])[C:49]2[C:44](=[CH:45][C:46]([F:54])=[CH:47][CH:48]=2)[N:43]=1.[C:55]1(=[O:61])[NH:60][CH2:59][CH2:58][CH2:57][CH2:56]1>CC(O)(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]>[Cl:53][C:50]1[C:49]2[C:44](=[CH:45][C:46]([F:54])=[CH:47][CH:48]=2)[N:43]=[C:42]([N:60]2[CH2:59][CH2:58][CH2:57][CH2:56][C:55]2=[O:61])[C:51]=1[CH3:52]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 126652-PiperidoneHCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphaneHCID 596311082,4-Dichloro-7-fluoro-3-methylquinoline

Product 1

HCID 67284990HCID 67284990, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Procedure

Freshly prepared powdered 3 Å molecular sieves were transferred to a round bottom flask and activated by heating under vacuum for 3 min. After this time the flask was allowed to cool to rt for 10 min. At this time, K2CO3 (601 mg, 4.35 mmol), 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-tri-i-propylbiphenyl (209 mg, 0.435 mmol), Pd2dba3 (199 mg, 0.217 mmol), 2,4-dichloro-7-fluoro-3-methylquinoline (500 mg, 2.173 mmol), delta-valerolactam (215 mg, 2.173 mmol) and the previously activated molecular sieves were suspended in tBuOH (4 mL) and heated in the microwave for 1 h at 150° C. After this time the reaction was partitioned between EtOAc (70 mL) and water (40 mL). The separated aqueous layer was extracted with EtOAc (40 mL) and the combined organic extracts were washed with water (20 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Column chromatography (hexanes:EtOAc, 1:0 to 2:1) gave 1-(4-chloro-7-fluoro-3-methylquinolin-2-yl)piperidin-2-one. 1H NMR (400 MHz, chloroform-d) δ ppm 8.12-8.29 (1H, m), 7.63 (1H, dd, J=9.8, 2.5 Hz), 7.35-7.47 (1H, m), 4.07-4.22 (1H, m), 3.39-3.53 (1H, m), 2.54-2.70 (2H, m), 2.35-2.50 (3H, m), 1.90-2.15 (4H, m). Mass Spectrum (ESI) m/e=293.0 (M+1).

Workup

  1. customFreshly prepared
  2. customwere transferred to a round bottom flask
  3. temperatureby heating under vacuum for 3 min
  4. temperatureheated in the microwave for 1 h at 150° C
  5. customAfter this time the reaction was partitioned between EtOAc (70 mL) and water (40 mL)
  6. extractionThe separated aqueous layer was extracted with EtOAc (40 mL)
  7. washthe combined organic extracts were washed with water (20 mL)
  8. dry with materialThe separated organic layer was dried over MgSO4
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-e748e7092a7b4f2c9fbdc5fcbb1416ec
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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