Ammonium Chloride → tert-Butyl 4-azido-3-hydroxypiperidine-1-carboxylate

HRID 1529556Notes

Reaction equation

HRID 1529556 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[CH3:5][C:6]([O:9][C:10]([N:12]1[CH2:18][CH2:17][CH:16]2[CH:14]([O:15]2)[CH2:13]1)=[O:11])([CH3:8])[CH3:7].[Cl-].[NH4+].C([O-])(O)=O.[Na+]>CCO.O>[CH3:8][C:6]([O:9][C:10]([N:12]1[CH2:18][CH2:17][CH:16]([N:1]=[N+:2]=[N-:3])[CH:14]([OH:15])[CH2:13]1)=[O:11])([CH3:5])[CH3:7].[CH3:8][C:6]([O:9][C:10]([N:12]1[CH2:18][CH2:17][CH:16]([OH:15])[CH:14]([N:1]=[N+:2]=[N-:3])[CH2:13]1)=[O:11])([CH3:5])[CH3:7]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 516892Sodium BicarbonateHCID 21991116tert-Butyl 7-Oxa-3-azabicyclo(4.1.0)heptane-3-carboxylate

Product 2

HCID 21874176tert-Butyl 4-azido-3-hydroxypiperidine-1-carboxylateYield 35%HCID 22392800Tert-butyl 3-azido-4-hydroxypiperidine-1-carboxylateYield 10%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

Sodium azide (0.94 g, 14.2 mmol) was added to a suspension of 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylic acid 1,1-dimethylethyl ester (2.18 g, 10.9 mmol) and ammonium chloride (0.76 g, 14.2 mmol) in a mixture of EtOH (11 mL) and H2O (11 mL). The mixture was stirred at 150° C. for 5 minutes under microwave irradiation. Then a saturated solution of NaHCO3 was added and the mixture was extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in Heptane 20/80 to 80/20). The desired fractions were collected and the solvents evaporated in vacuo to yield 4-azido-3-hydroxy-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (0.93 g, 35% yield) and 3-azido-4-hydroxy-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (0.26 g, 10% yield).

Workup

  1. extractionthe mixture was extracted with DCM
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica; AcOEt in Heptane 20/80 to 80/20)
  7. customThe desired fractions were collected
  8. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-b6d18aae3854454ea498f4ec31247565
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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