Trifluoroacetic acid → HCID 59452754, compound

HRID 419347Notes

Reaction equation

HRID 419347 reaction equation
[N:1]1([CH2:7][CH:8]2[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=O)[CH2:10][CH2:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O.[CH3:28][O:29][C:30]1[CH:35]=C(F)[CH:33]=[CH:32][C:31]=1[N+:37]([O-:39])=[O:38].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CS(C)=O.CCOC(C)=O>[CH3:28][O:29][C:30]1[CH:35]=[C:14]([N:11]2[CH2:10][CH2:9][CH:8]([CH2:7][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[CH2:13][CH2:12]2)[CH:33]=[CH:32][C:31]=1[N+:37]([O-:39])=[O:38]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 27792505-Fluoro-2-nitroanisoleHCID 539146451-Boc-4-Piperidin-1-ylmethyl-piperidine

Product 1

HCID 59452754HCID 59452754, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,1-dimethylethyl 4-(1-piperidinylmethyl)-1-piperidinecarboxylate (1.25 g, 4.43 mmol) in DCM (40 mL) was cooled with an ice/H2O bath. TFA (8.80 mL, 115 mmol) was added dropwise via pipette. Upon completion by TLC the reaction was quenched with 1N NaOH (115 mL) and extracted with EtOAc. The combined organic layer was washed with brine, dried (MgSO4) and concentrated. The combined aqueous layer was treated with 1N NaOH, extracted with DCE/iso-propanol (4:1), dried (MgSO4) and concentrated. The crude material was added to 5-fluoro-2-nitrophenyl methyl ether (Example 22, step A) (0.833 g, 4.87 mmol) and K2CO3 (0.992 g, 7.17 mmol) in DMSO (15 mL) and stirred at rt overnight. Upon completion by TLC, the reaction was diluted with EtOAc (250 mL), washed with H2O (three times), dried (MgSO4) and concentrated. Purification by flash chromatography provided the title compound (0.890 g, 2.66 mmol, 60% over two steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.04-1.14 (m, 2H), 1.30-1.41 (m, 2H), 1.42-1.50 (m, 4H), 1.72-1.83 (m, 3H), 2.07 (d, J=7.0 Hz, 2H), 2.27 (br. s., 4H), 2.93 (td, J=12.7, 2.2 Hz, 2H), 3.88 (s, 3H), 4.00 (d, J=13.6 Hz, 2H), 6.45 (d, J=2.6 Hz, 1H), 6.55 (dd, J=9.5, 2.6 Hz, 1H), 7.85 (d, J=9.5 Hz, 1H).

Workup

  1. customUpon completion by TLC the reaction was quenched with 1N NaOH (115 mL)
  2. extractionextracted with EtOAc
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. additionThe combined aqueous layer was treated with 1N NaOH
  7. extractionextracted with DCE/iso-propanol (4:1)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. washwashed with H2O (three times)
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customPurification by flash chromatography

Sources & evidence

ORD record
ord-ece978784d48429fa5a42c62bef0e670
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…