Hydrochloric Acid → 1-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-amine

HRID 2421977Notes

Reaction equation

HRID 2421977 reaction equation
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[CH:16][N:15]=2)[CH2:10][CH2:9]1)(C)(C)C.CO.Cl>C1COCC1.O1CCOCC1>[Cl:20][C:19]1[C:14]([N:11]2[CH2:10][CH2:9][CH:8]([NH2:7])[CH2:13][CH2:12]2)=[N:15][CH:16]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:18]=1

Participants

6

Reactant 3

HCID 313Hydrochloric Acid3×HCID 887MethanolHCID 2796148Tert-butyl (1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperidin-4-yl)carbamate

Product 1

HCID 27961851-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-amineYield 128.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent3×

Procedure

tert-Butyl{1-[3-chloro-5-(trifluoromethyl)pyridine-2-yl]piperidin-4-yl}carbamate (2.5 g, 6.4 mmol) was stirred in a mixture of THF (25 ml), MeOH (5 ml) and HCl in dioxane (4M, 6.5 ml) over night at rt. HCl in dioxane (4M, 4 ml) was added and after 4 h a third portion of HCl in dioxane/4M, 4 ml) was added. Stirring was continued for 48 h at rt. The solvent was evaporated, and the residue was dissolved in EtOAc. The resulting mixture was washed with aqueous saturated Na2CO3, water and dried over Na2SO4. Concentration of the organic phase yielded the title compound (2.3 g, 128%), which contained some impurities. 1H NMR (500 MHz, CDCl3): δ 1.50-1.54 (m, 2H), 1.88-1.94 (m, 2H), 2.93-3.00 (m, 3H), 4.01-4.04 (m, 2H), 7.74 (s, 1H), 8.38 (s, 1H); Mass Spectrum: M+H+ 280.

Workup

  1. additionwas added
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in EtOAc
  4. washThe resulting mixture was washed with aqueous saturated Na2CO3, water
  5. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-648562df9bf94f6da6f5cf8bf9cb6bf9
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Reaction notes

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