Trifluoroacetic acid → HCID 53954167, compound

HRID 1667203Notes

Reaction equation

HRID 1667203 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4][CH2:3]1.Cl.[CH2:16]([O:23][NH2:24])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.FC(F)(F)C(O)=O>N1C=CC=CC=1.C(Cl)Cl>[CH2:16]([O:23][N:24]=[C:2]1[CH2:3][CH2:4][NH:5][CH2:6][CH2:7]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 102312Benzyloxyamine hydrochlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 53954167HCID 53954167, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 4-oxopiperidine-1-carboxylate (524 mg, 2.63 mmol) and O-benzylhydroxylamine hydrochloride (504 mg, 3.16 mmol) in pyridine (5 mL) was stirred at ambient temperature for 18 hours. The reaction mixture was concentrated in vacuo and the residue was partitioned between ether and H2O. The separated organic phase was washed with 1 N aqueous HCl and brine, dried over MgSO4, filtered, and concentrated in vacuo to yield 816 mg of crude N-tert-butoxycarbonyl intermediate. This material was taken up in CH2Cl2 (5 mL), followed by addition of trifluoroacetic acid (5.0 mL, 65.0 mmol) via syringe. After stirring for 30 minutes at ambient temperature, the reaction was cooled to 0° C. and quenched by slow addition of 2 N aqueous NaOH solution (35 mL). The mixture was diluted with 75 mL CH2Cl2 and the phases were separated. The organic layer was washed with 1 N aqueous NaOH solution and brine, dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.39-7.27 (m, 5H), 5.07 (s, 2H), 3.02-2.94 (m, 2H), 2.94-2.86 (m, 2H), 2.63-2.54 (m, 2H), 2.33-2.23 (m, 2H), 1.58 (bs, 1H); MS (DCI+) m/z 205 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between ether and H2O
  3. washThe separated organic phase was washed with 1 N aqueous HCl and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto yield 816 mg of crude N-tert-butoxycarbonyl intermediate
  8. temperaturethe reaction was cooled to 0° C.
  9. customquenched by slow addition of 2 N aqueous NaOH solution (35 mL)
  10. additionThe mixture was diluted with 75 mL CH2Cl2
  11. customthe phases were separated
  12. washThe organic layer was washed with 1 N aqueous NaOH solution and brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-89d301bc463c45238c91d1fbe463da25
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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