Ethyl Acetate → tert-butyl 4-{2-[4-(2-cyano-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenoxy]ethyl}piperidine-1-carboxylate

HRID 522255Notes

Reaction equation

HRID 522255 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.Cl[C:23]1[N:24]=[C:25]([C:33]2[CH:54]=[CH:53][C:36]([O:37][CH2:38][CH2:39][CH:40]3[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH2:41]3)=[C:35]([C:55]([F:58])([F:57])[F:56])[CH:34]=2)[C:26]2[CH:31]=[CH:30][N:29]([CH3:32])[C:27]=2[N:28]=1.CCOC(C)=O.C[C:66]([N:68](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:66]([C:23]1[N:24]=[C:25]([C:33]2[CH:54]=[CH:53][C:36]([O:37][CH2:38][CH2:39][CH:40]3[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH2:41]3)=[C:35]([C:55]([F:58])([F:57])[F:56])[CH:34]=2)[C:26]2[CH:31]=[CH:30][N:29]([CH3:32])[C:27]=2[N:28]=1)#[N:68]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 31374DimethylacetamideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 117899634tert-butyl 4-{2-[4-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenoxy]ethyl}piperidine-1-carboxylate

Product 1

HCID 90065710tert-butyl 4-{2-[4-(2-cyano-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenoxy]ethyl}piperidine-1-carboxylate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

Zinc (29 mg), 2-(di-tert-butylphosphino)biphenyl (59 mg), zinc cyanide (63 mg), and palladium (II) trifluoroacetate (30 mg) were added to a solution of tert-butyl 4-{2-[4-(2-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenoxy]ethyl}piperidine-1-carboxylate (480 mg) in DMAc (10 mL) at room temperature in an argon atmosphere, and the mixture was stirred at 110° C. for 5 hours. After the reaction mixture was cooled to room temperature, EtOAc was added thereto, followed by stirring, and the insoluble material was separated by filtration using Celite. This filtrate was washed with a saturated aqueous NaHCO3 solution, 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=9:1 to 1:1), whereby tert-butyl 4-{2-[4-(2-cyano-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-2-(trifluoromethyl)phenoxy]ethyl}piperidine-1-carboxylate (236 mg) was obtained as a light yellow solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringby stirring
  3. customthe insoluble material was separated by filtration
  4. washThis filtrate was washed with a saturated aqueous NaHCO3 solution, water, and saturated brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=9:1 to 1:1)

Sources & evidence

ORD record
ord-803e6d0efc92435cb5279781b6e69d7d
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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