4-(N-Boc-amino)piperidine → Tert-butyl {1-[4-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)carbamate

HRID 2421985Notes

Reaction equation

HRID 2421985 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[NH:12]1[CH2:17][CH2:16][CH:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:14][CH2:13]1>CS(C)=O>[F:9][C:8]([F:11])([F:10])[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:12]2[CH2:13][CH2:14][CH:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])[CH2:16][CH2:17]2)[CH:7]=1

Participants

4

Reactant 2

HCID 7238334-(N-Boc-amino)piperidineHCID 27815432-Bromo-4-(trifluoromethyl)pyridine

Product 1

HCID 86625877Tert-butyl {1-[4-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)carbamateYield 71%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 2-bromo-4-trifluoromethylpyridine (1.00 g, 4.42 mmol), tert-butyl piperidine-4-ylcarbamate (0.93 g, 4.65 mmol) and TEA (0.67 mL, 4.86 mmol) in DMSO (5 L) was heated at 120° C. for 17 h. The reaction mixture was evaporated to dryness, Et2O was added, and the organic phase was washed with water, brine and evaporated to dryness. The residue was purified using the Biotage Horizon HPFC system eluting with 22% EtOAc in petroleum ether (40-60° C.) to give the title compound (1.08 g, 71%) as a solid. 1H NMR (500 MHz, CDCl3): 8.30 (d, 1H), 6.82 (s, 1H), 6.77 (d, 1H), 4.49 (bs, 1H), 4.36-4.22 (m, 2H), 3.74 (bs, 1H), 3.06 (td, 2H), 2.10-2.04 (m, 2H), 1.56-1.38 (m, 11H); 13C NMR (CDCl3): 159.4, 155.4, 149.5, 140.1, 139.9, 124.5, 122.4, 108.1, 102.7, 79.8, 48.3, 44.4, 32.3, 28.6; Mass Spectrum: M+H 346.

Workup

  1. customThe reaction mixture was evaporated to dryness, Et2O
  2. additionwas added
  3. washthe organic phase was washed with water, brine
  4. customevaporated to dryness
  5. customThe residue was purified
  6. washeluting with 22% EtOAc in petroleum ether (40-60° C.)

Sources & evidence

ORD record
ord-e0cc3926c7fd426caf56091fd4d6f00a
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Reaction notes

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