Dichloromethane → HCID 57803361, compound

HRID 2367034Notes

Reaction equation

HRID 2367034 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH3:10])=[O:8])[CH2:3][CH2:2]1.Br[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1.CC(C)([O-])C.[K+].ClCCl>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.Cl[Pd]Cl.[Fe+2].CN(C=O)C.C1(C)C=CC=CC=1>[F:19][C:18]([F:21])([F:20])[C:14]1[CH:13]=[C:12]([N:1]2[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH3:10])=[O:8])[CH2:3][CH2:2]2)[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 9817Benzene, 1-bromo-3-(trifluoromethyl)-HCID 424914Methyl isonipecotateHCID 23665647Potassium tert-butoxide

Product 1

HCID 57803361HCID 57803361, compoundYield 46.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

Methyl piperidine-4-carboxylate (2.0 g, 14 mmol), 1-bromo-3-(trifluoromethyl)benzene (1.5 g, 6.8 mmol), and potassium tert-butoxide (0.76 g, 6.8 mmol) in a mixed solvent of toluene (20 mL) and DMF (4 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.3 g, 0.4 mmol) under nitrogen. The mixture was heated at 130° C. in an oil bath overnight. After cooling to room temperature, the mixture was filtered through celite and diluted with EtOAc. The resulting solution was washed with saturated NaHCO3. The aqueous layer was extracted with EtOAc twice. The combined organic layers were dried (MgSO4), concentrated and flash chromatographed with EtOAc/hexanes (20% to 40%) to give 0.90 g of product. MS (M+H) 288.2.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered through celite
  3. additiondiluted with EtOAc
  4. washThe resulting solution was washed with saturated NaHCO3
  5. extractionThe aqueous layer was extracted with EtOAc twice
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated
  8. customflash chromatographed with EtOAc/hexanes (20% to 40%)

Sources & evidence

ORD record
ord-7ca0d0e54bdd40c58dec06c454997cbd
Source dataset
uspto-grants-2014_04
Patent number
US08697870B2

Reaction notes

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