4-(Trifluoromethyl)aniline → 1-Boc-4-(4-Trifluoromethyl-phenylamino)-piperidine

HRID 1667206Notes

Reaction equation

HRID 1667206 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1.O=[C:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.[O-]S([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].[OH-].[Na+]>C(O)(=O)C>[F:1][C:2]([F:10])([F:11])[C:3]1[CH:9]=[CH:8][C:6]([NH:7][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[CH:5][CH:4]=1

Participants

8

Reactant 6

HCID 99644-(Trifluoromethyl)anilineHCID 14798Sodium HydroxideHCID 24436Sodium SulfateHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 220291421-Boc-4-(4-Trifluoromethyl-phenylamino)-piperidine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 4-(trifluoromethyl)aniline (0.772 mL, 6.21 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (2.47 g, 12.4 mmol) in acetic acid (30 mL) was treated with anhydrous Na2SO4 powder (8.82 g, 62.1 mmol). The mixture was stirred at ambient temperature for 20 minutes, and then sodium triacetoxyborohydride (3.95 g, 18.6 mmol) was added in approximately 5 equal portions over 2 minutes. The reaction was allowed to proceed at ambient temperature for 3 hours. The reaction mixture was carefully poured into a well-stirred mixture of 1:1 ethyl acetate/hexanes (100 mL) and saturated NaHCO3 solution (150 mL), and then basified with excess 2 N aqueous NaOH solution. The phases were separated, and the organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was triturated with hexanes and the solid was collected by vacuum filtration and air-dried to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.35 (d, J=8.6, 2H), 6.69 (d, J=8.6, 2H), 6.25 (d, J=8.0, 1H), 3.95-3.80 (m, 2H), 3.56-3.40 (m, 1H), 3.02-2.81 (m, 2H), 1.94-1.80 (m, 2H), 1.40 (s, 9H), 1.33-1.18 (m, 2H); MS (DCI+) m/z 345 (M+H)+.

Workup

  1. waitto proceed at ambient temperature for 3 hours
  2. customThe phases were separated
  3. washthe organic layer was washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was triturated with hexanes
  8. filtrationthe solid was collected by vacuum filtration
  9. customair-dried

Sources & evidence

ORD record
ord-7799693e9cac496e9a5746da95bdd308
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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