Nitrogen → Tert-butyl 4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidine-1-carboxylate

HRID 58490Notes

Reaction equation

HRID 58490 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]=2)=[C:4]([C:21]([F:24])([F:23])[F:22])[CH:3]=1.N#N>C(OCC)(=O)C.[Pt](=O)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]2)=[C:4]([C:21]([F:24])([F:22])[F:23])[CH:3]=1

Participants

5

Reactant 2

HCID 947NitrogenHCID 118483328HCID 118483328, compound

Product 1

HCID 118483512Tert-butyl 4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidine-1-carboxylateYield 63%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 4-(4-fluoro-2-(tri-fluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (1.29 g, 3.74 mmol) in ethyl acetate (20 mL) andacetic acid (0.22 mL) was sparged with N2. Platinum dioxide (84 mg) was added and the resulting suspension was sparged with N2 for 5 min. The mixture was placed under an H2 atmosphere at 1 atm. After 18 h the reaction was sparged with N2 for 15 min, filtered through a diatomaceous earth pad, recharged with platinum dioxide (100 mg) and stirred under a 1 atm hydrogen atmosphere. The filtration and recharging of the reaction was repeated thrice over the next 64 h. The reaction was filtered through diatomaceous earth. The obtained filtrate was washed with sodium bicarbonate solution, dried (Na2SO4) and concentrated under reduced pressure. The residue was chromatographed over silica gel (Isco CombiFlash Rf unit, 24 g Redisep column, 0% to 100% EtOAc in hexanes) to provide tert-butyl 4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidine-1-carboxylate as a yellow oil (0.813 g, 63%): 1H NMR (300 MHz, CDCl3) δ 7.37-7.20 (m, 3H), 4.27-4.22 (m, 2H), 3.07-2.99 (m, 1H), 2.85-2.75 (m, 2H), 2.04-1.46 (m, 13H).

Workup

  1. customthe resulting suspension was sparged with N2 for 5 min
  2. customAfter 18 h the reaction was sparged with N2 for 15 min
  3. filtrationfiltered through a diatomaceous earth pad
  4. filtrationThe filtration and recharging of the reaction
  5. customover the next 64 h
  6. filtrationThe reaction was filtered through diatomaceous earth
  7. washThe obtained filtrate was washed with sodium bicarbonate solution
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was chromatographed over silica gel (Isco CombiFlash Rf unit, 24 g Redisep column, 0% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2359e1314b3e4bc1873b0bc6a267747e
Source dataset
uspto-grants-2016_09
Patent number
US09434727B2

Reaction notes

Loading…