Ethyl Acetate → tert-butyl 4-(2-{[5-(2-cyano-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate

HRID 522284Notes

Reaction equation

HRID 522284 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl[C:32]1[N:40]=[C:39]2[C:35]([N:36]=[CH:37][N:38]2[CH3:41])=[C:34]([C:42]2[CH:43]=[C:44]([C:64]([F:67])([F:66])[F:65])[C:45]([O:48][CH2:49][CH2:50][CH:51]3[CH2:56][CH2:55][N:54]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:53][CH2:52]3)=[N:46][CH:47]=2)[N:33]=1.CCOC(C)=O.C[C:75]([N:77](C)C)=O>[Zn].[C-]#N.[Zn+2].[C-]#N.FC(F)(F)C([O-])=O.[Pd+2].FC(F)(F)C([O-])=O>[C:75]([C:32]1[N:40]=[C:39]2[C:35]([N:36]=[CH:37][N:38]2[CH3:41])=[C:34]([C:42]2[CH:43]=[C:44]([C:64]([F:67])([F:66])[F:65])[C:45]([O:48][CH2:49][CH2:50][CH:51]3[CH2:56][CH2:55][N:54]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:53][CH2:52]3)=[N:46][CH:47]=2)[N:33]=1)#[N:77]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 31374DimethylacetamideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 117899621tert-butyl 4-(2-{[5-(2-chloro-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate

Product 1

HCID 117899570tert-butyl 4-(2-{[5-(2-cyano-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 2733347Palladium(II) trifluoroacetateCatalyst

Conditions

Temperature
50 °C

Procedure

Zinc (498 mg), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (1.3 g), zinc cyanide (1.8 g), and palladium (II) trifluoroacetate (498 mg) were added to a solution of tert-butyl 4-(2-{[5-(2-chloro-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate (8.3 g) in DMAc (125 mL) at room temperature in an argon atmosphere, and the mixture was stirred at 50° C. for 3 hours. After the reaction mixture was cooled to room temperature, EtOAc (100 mL) and Celite were added thereto, and the mixture was stirred at room temperature. The insoluble material was separated by filtration, and a saturated aqueous NaHCO3 solution, saturated brine, and water was added to the filtrate. Extraction was performed on the mixture using EtOAc, and the extract was washed with water and saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=70:30 to 30:70), whereby tert-butyl 4-(2-{[5-(2-cyano-9-methyl-9H-purin-6-yl)-3-(trifluoromethyl)pyridin-2-yl]oxy}ethyl)piperidine-1-carboxylate (7.6 g) was obtained as a solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred at room temperature
  3. customThe insoluble material was separated by filtration
  4. additiona saturated aqueous NaHCO3 solution, saturated brine, and water was added to the filtrate
  5. extractionExtraction
  6. washthe extract was washed with water and saturated brine
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=70:30 to 30:70)

Sources & evidence

ORD record
ord-1e526a21ad1449bdb21f4f8ccc4c4ad8
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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