Trifluoroacetic acid → 1-(4-Chloro-3-fluorobenzyl)-4-piperidinamine

HRID 1070512Notes

Reaction equation

HRID 1070512 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([NH:13]C(=O)OC(C)(C)C)[CH2:9][CH2:8]2)=[CH:4][C:3]=1[F:23].FC(F)(F)C(O)=O.[OH-].[Na+]>ClCCl>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]2)=[CH:4][C:3]=1[F:23]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 68886889Tert-butyl 1-(4-chloro-3-fluorobenzyl)-4-piperidinylcarbamate

Product 1

HCID 223962051-(4-Chloro-3-fluorobenzyl)-4-piperidinamineYield 39.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 1-(4-chloro-3-fluorobenzyl)-4-piperidinylcarbamate (1.80 g) in dichloromethane (20 ml) was stirred under nitrogen. Trifluoroacetic acid (5 ml) was then added dropwise and the reaction was left to stir for 2 hours. 1M sodium hydroxide was added to the reaction until basic, with the resulting solution being extracted three times with dichloromethane. The pooled organic phases were washed once with water, once with brine, dried over magnesium sulfate, filtered and the solvent removed under reduced pressure. Product purified by chromatography (5% ethanol/dichloromethane to 10% ethanol/dichloromethane) and solvent removed under reduced pressure to leave an oil which crystallised over the period of 48 hours. The resulting solid was triturated with diethyl ether and filtered to leave 1-(4-chloro-3-fluorobenzyl)-4-piperidinamine (0.500 g) as a white solid.

Workup

  1. waitthe reaction was left
  2. extractionbeing extracted three times with dichloromethane
  3. washThe pooled organic phases were washed once with water, once with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customProduct purified by chromatography (5% ethanol/dichloromethane to 10% ethanol/dichloromethane) and solvent
  8. customremoved under reduced pressure
  9. customto leave an oil which
  10. customcrystallised over the period of 48 hours
  11. customThe resulting solid was triturated with diethyl ether
  12. filtrationfiltered

Sources & evidence

ORD record
ord-69961bf7d78d4f4392260ce4349da5cc
Source dataset
uspto-grants-2005_06
Patent number
US06903085B1

Reaction notes

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