p-Toluenesulfonic acid → HCID 58699966, compound

HRID 970368Notes

Reaction equation

HRID 970368 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10]([C:15]([F:18])([F:17])[F:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:19][C@@H:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:27][C@@H:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH3:19])[C@H:10]([C:15]([F:18])([F:17])[F:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6431891-Phenethylamine, (+)-HCID 4311764Sodium borohydrideHCID 21054730tert-Butyl 4-oxo-3-(trifluoromethyl)piperidine-1-carboxylate

Product 1

HCID 58699966HCID 58699966, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of (±)-4-oxo-3-(trifluoromethyl)piperidine-1-carboxylic acid tert-butyl ester (2b) (1 equiv.) in toluene is added (R)-(+)-α-methylbenzylamine (1 equiv.) and catalytic amount of p-toluenesulfonic acid. The solution is heated to reflux under a Dean-Stark apparatus. After 12 hr, the reaction is cooled to RT, washed with 10% aqueous NaHCO3, dried over Na2SO4, and concentrated in vacuo. The residue is dissolved in EtOH and NaBH4 (1 equiv.) is added. After 12 h, the reaction is concentrated and the residue is dissolved in 1 N HCl. The solution is neutralized with 6 N NaOH and extracted with EtOAc. The organic fraction is dried over Na2SO4 and concentrated under vacuum. The crude product is purified by chromatography on silica gel to afford the title compound. The three other diastereomers are also separated.

Workup

  1. temperatureThe solution is heated
  2. temperatureto reflux under a Dean-Stark apparatus
  3. washwashed with 10% aqueous NaHCO3
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue is dissolved in EtOH
  7. waitAfter 12 h
  8. concentrationthe reaction is concentrated
  9. dissolutionthe residue is dissolved in 1 N HCl
  10. extractionextracted with EtOAc
  11. dry with materialThe organic fraction is dried over Na2SO4
  12. concentrationconcentrated under vacuum
  13. customThe crude product is purified by chromatography on silica gel

Sources & evidence

ORD record
ord-c342a6f6febd4e818a72c8b304ce84ab
Source dataset
uspto-grants-2007_12
Patent number
US07312212B2

Reaction notes

Loading…