1,2-Dichloroethane → Tert-butyl 4-[(5-chloro-2-hydroxypiperidin-3-yl)amino]piperidine-1-carboxylate

HRID 1026548Notes

Reaction equation

HRID 1026548 reaction equation
ClCCCl.[NH2:5][C:6]1[C:7]([OH:13])=[N:8][CH:9]=[C:10]([Cl:12])[CH:11]=1.O=[C:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.O>[Cl:12][CH:10]1[CH2:9][NH:8][CH:7]([OH:13])[CH:6]([NH:5][CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH2:11]1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate2×HCID 5049666Sodium triacetoxyborohydride2×HCID 178507679HCID 178507679, compound

Product 1

HCID 68006279Tert-butyl 4-[(5-chloro-2-hydroxypiperidin-3-yl)amino]piperidine-1-carboxylateYield 62.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a 1,2-dichloroethane suspension (177 ml) of 3-amino-5-chloropyridin-2-ol (8.85 g) and tert-butyl 4-oxopiperidine-1-carboxylate (24.4 g) was added sodium triacetoxyborohydride (26.0 g), followed by stirring under heating at reflux for 4 hours. Tert-butyl 4-oxopiperidine-1-carboxylate (12.4 g) and sodium triacetoxyborohydride (13.7 g) were further added, and stirred under heating at reflux for 2 hours. After the reaction solution was brought back to room temperature, water and dichloromethane were added, and the solution was separated. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford tert-butyl 4-[(5-chloro-2-hydroxypiperidin-3-yl)amino]piperidine-1-carboxylate (12.7 g).

Workup

  1. temperatureunder heating
  2. temperatureat reflux for 4 hours
  3. stirringstirred
  4. temperatureunder heating
  5. temperatureat reflux for 2 hours
  6. customwas brought back to room temperature
  7. customthe solution was separated
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-e808f8802edc46c28c0443fc3386bf8b
Source dataset
uspto-grants-2014_05
Patent number
US08729095B2

Reaction notes

Loading…