3-(Trifluoromethyl)aniline → 1-Boc-4-(3-trifluoromethyl-phenylamino)-piperidine

HRID 43348Notes

Reaction equation

HRID 43348 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[F:15][C:16]([F:25])([F:24])[C:17]1[CH:18]=[C:19]([CH:21]=[CH:22][CH:23]=1)[NH2:20].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[F:15][C:16]([F:24])([F:25])[C:17]1[CH:18]=[C:19]([NH:20][CH:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]2)[CH:21]=[CH:22][CH:23]=1

Participants

6

Reactant 4

HCID 73753-(Trifluoromethyl)anilineHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 37223301-Boc-4-(3-trifluoromethyl-phenylamino)-piperidineYield 99.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A Solution of 1,1-Dimethylethyl 4-Oxo-1-Piperidinecarboxylate (0.5 g, 2.5 mmol), 3-(trifluoromethyl)aniline (0.402 g, 2.5 mmol) and sodium tri(acetoxy)borohydride (0.80 g, 3.75 mmol) in 1,2-DCE (5 ml) was stirred at room temperature, under argon overnight. Saturated aq. NaHCO3 solution (15 ml) was added and stirring continued for 1 h. The reaction mixture was extracted with DCM and the organic phase concentrated in vacuo. Recrystallisation of the solid residue gave the title compound as a white solid (0.86 g). δH (CDCl3, 250 MHz)) 7.25 (1H, t), 6.92 (1H, d), 6.75 (2H, m), 4.06 (2H, m), 3.45 (1H, m), 2.94 (2H, m), 2.04 (2H, m), 1.46 (9H, s), 1.36 (2H, m).

Workup

  1. extractionThe reaction mixture was extracted with DCM
  2. concentrationthe organic phase concentrated in vacuo
  3. customRecrystallisation of the solid residue

Sources & evidence

ORD record
ord-0341eb119a7e42ef945e757759224d7c
Source dataset
uspto-grants-2013_09
Patent number
US08536182B2

Reaction notes

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