Pyridine → Tert-butyl 3-(5-(4-fluorophenyl)oxazol-2-yl)piperidine-1-carboxylate

HRID 874996Notes

Reaction equation

HRID 874996 reaction equation
N1C=CC=CC=1.[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:32])[CH2:15][NH:16][C:17]([CH:19]2[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]2)=O)=[CH:10][CH:9]=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(Cl)Cl>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[O:32][C:17]([CH:19]3[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:20]3)=[N:16][CH:15]=2)=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 69935617Tert-butyl 3-((2-(4-fluorophenyl)-2-oxoethyl)carbamoyl)piperidine-1-carboxylate

Product 1

HCID 69935244Tert-butyl 3-(5-(4-fluorophenyl)oxazol-2-yl)piperidine-1-carboxylateYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Dry pyridine (0.24 mL, 2.74 mmol) was added dropwise to a solution of tert-butyl 3-((2-(4-fluorophenyl)-2-oxoethyl)carbamoyl)piperidine-1-carboxylate (500 mg, 1.37 mmol) in dry CH2Cl2 (12 mL) at 0° C., followed by trifluoromethanesulfonic anhydride (0.5 mL, 2.74 mmol). The reaction mixture was allowed to warm up to room temperature and stirred for 3 h. The reaction mixture was diluted with CH2Cl2 and the organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by purified by column chromatography (silica gel 60-120 mesh, eluent 12-15% EtOAc in petroleum ether) to afford tert-butyl 3-(5-(4-fluorophenyl)oxazol-2-yl)piperidine-1-carboxylate (150 mg, yield 32%). 1H NMR (400 MHz, DMSO-d6) δ 7.75-7.72 (dd, J=9.0 Hz, 5.3 Hz, 2H), 7.55 (s, 1H), 7.33-7.29 (t, J=8.8 Hz, 2H), 3.99-3.90 (m, 1H), 3.69-3.60 (m, 1H), 3.02 (m, 1H), 2.12-2.07 (m, 1H), 1.82-1.76 (m, 2H), 1.64-1.57 (m, 1H), 1.51-1.42 (m, 2H), 1.35 (s, 9H). MS (ESI) m/z: Calculated for C19H23FN2O3: 346.17. found: 347.2 (M+H)+

Workup

  1. washthe organic layer was washed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified
  5. customby purified by column chromatography (silica gel 60-120 mesh, eluent 12-15% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-0d86d51b182c4a06b9a6d5278530df28
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

Loading…