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

HRID 962720Notes

Reaction equation

HRID 962720 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[OH:22].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(OCC)(=O)C.C(O)(=O)C.ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[OH:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 58012-AminophenolHCID 516892Sodium BicarbonateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 22380697tert-Butyl 4-(2-hydroxyanilino)piperidine-1-carboxylateYield 79%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6.0 g N-t-butyloxycarbonyl-4-piperidone, 3.3 g of 2-aminophenol, 25 mL of 1,2-dichloroethane, 25 mL of glacial acetic acid, and 500 mg powdered 4 Å molecular sieves was stirred under inert atmosphere. After 30 min, 6.4 g sodium triacetoxyborohydride was added stirring was continued for 38 h. The reaction mixture was poured into 400 mL ethyl acetate and 200 mL saturated aqueous NaHCO3 and the layers separated. The organic layer was washed with brine (2×100 mL), dried over MgSO4, filtered and concentrated under reduced pressure. Chromatography of the crude product on silica gel, eluting with a gradient of 1-3% methanol/methylene chloride containing 0.5% concentrated NH4 OH gave 6.95 g (79%) 1-t-butyloxycarbonyl-4-(2-hydroxyphenylamino)piperidine as an orange foam.

Workup

  1. stirringstirring
  2. waitwas continued for 38 h
  3. customthe layers separated
  4. washThe organic layer was washed with brine (2×100 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. washChromatography of the crude product on silica gel, eluting with a gradient of 1-3% methanol/methylene chloride containing 0.5% concentrated NH4 OH

Sources & evidence

ORD record
ord-f236359c2e9b4d14a0cb5b6e0a3cf74c
Source dataset
uspto-grants-1998_06
Patent number
US05760054

Reaction notes

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