Tetrahydrofuran → HCID 68733876, compound

HRID 2382183Notes

Reaction equation

HRID 2382183 reaction equation
[C:1]1([NH:7][CH:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1.CC(C)([O-])C.[K+].O1CCCC1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]1([N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)[CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 67868Benzene, 1-iodo-3-(trifluoromethyl)-HCID 14915021-Boc-4-APHCID 23665647Potassium tert-butoxide

Product 1

HCID 68733876HCID 68733876, compoundYield 58.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of tert-butyl 4-(phenylamino)piperidine-1-carboxylate (2.30 g, 8 mmol), 1-iodo-3-(trifluoromethyl)benzene (1 ml, 8 mmol), palladium(ii) acetate (0.07 g, 0.3 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.2 g, 0.3 mmol), and potassium tert-butoxide, 1.0M solution in tetrahydrofuran (1 ml, 10 mmol) in toluene (20 mL) was heated at 110° C. for 18 h. The reaction mixture was diluted with EtOAc, filtered, washed with 1N NaOH and brine, and the organic layer was concentrated under vacuum. Conc HCl (20 mL) was added to the residue and the solution was concentrated under vacuum. Conc HCl (20 mL) was added to the residue and the solution was stirred at RT for 8 h and concentrated. The pH was adjusted to 11 with the addition of 1N NaOH solution and the product was extracted with DCM. The DCM layer was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified with ISCO using 0-15% MeOH in DCM to give product N-phenyl-N-(3-(trifluoromethyl)phenyl)piperidin-4-amine (1.5 g, 56% yield).

Workup

  1. filtrationfiltered
  2. washwashed with 1N NaOH and brine
  3. concentrationthe organic layer was concentrated under vacuum
  4. additionConc HCl (20 mL) was added to the residue
  5. concentrationthe solution was concentrated under vacuum
  6. additionConc HCl (20 mL) was added to the residue
  7. concentrationconcentrated
  8. additionThe pH was adjusted to 11 with the addition of 1N NaOH solution
  9. extractionthe product was extracted with DCM
  10. dry with materialThe DCM layer was dried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified with ISCO

Sources & evidence

ORD record
ord-45914936de8c41caa1015adebfc4c159
Source dataset
uspto-grants-2012_09
Patent number
US08258306B2

Reaction notes

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