Acetic Acid → tert-Butyl 4-(2-hydroxyanilino)piperidine-1-carboxylate

HRID 1377679Notes

Reaction equation

HRID 1377679 reaction equation
[OH:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].CC(O)=O.[BH3-]C#N.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.O>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH:4][C:3]2[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=2[OH:1])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 58012-AminophenolHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 22380697tert-Butyl 4-(2-hydroxyanilino)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-hydroxyaniline (5.0 g, 46 mmol), N-t-butyloxycarbonyl-4-piperidinone (9.05 g, 46 mmol) and HOAc (5.7 mL, 100 mmol) in dry toluene (250 mL) was refluxed with azeotropic removal of water for 24 h. The solution was cooled to ambient temperature and to it was added NaCNBH3 (5.8 g, 92 mmol). The resulting mixture was stirred at ambient temperature for 24 h. EtOAc (250 mL) was added and the solution was washed with saturated aqueous NaHCO3 (4×100 mL). The organic phase was dried (MgSO4), filtered, and the solvents were removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using a gradient elution of 15-25% EtOAc-hexanes. 1-t-Butyloxycarbonyl-4-(2-hydroxyphenylamino)piperidine was obtained as a solid (45% yield).

Workup

  1. washthe solution was washed with saturated aqueous NaHCO3 (4×100 mL)
  2. dry with materialThe organic phase was dried (MgSO4)
  3. filtrationfiltered
  4. customthe solvents were removed under reduced pressure
  5. customThe residue was purified by pressurized silica gel column chromatography
  6. washa gradient elution of 15-25% EtOAc-hexanes

Sources & evidence

ORD record
ord-cf3e15238859431a8e251cf98a6babc0
Source dataset
uspto-grants-1997_09
Patent number
US05665719

Reaction notes

Loading…