Ammonium Chloride → (3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 2066540Notes

Reaction equation

HRID 2066540 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH:12]2[CH:10]([O:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:15]=[N+:16]=[N-:17].[Na+].[Cl-].[NH4+]>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C@@H:12]([N:15]=[N+:16]=[N-:17])[C@H:10]([OH:11])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C@H:12]([OH:11])[C@@H:10]([N:15]=[N+:16]=[N-:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

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

Product 2

HCID 58745530(3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl esterHCID 86650186HCID 86650186, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirring solution of (±)-7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (2.4 g, 12.06 mmol) in ethanol (20 mL) was added sodium azide (1.00 g, 15.62 mmol) and ammonium chloride (840 mg, 15.79 mmol). The resulting mixture was heated to reflux overnight and then partitioned between ethyl acetate and water. The combined organic layers were washed with brine, separated and dried (MgSO4). The crude product was purified by column chromatography to yield (3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (1.95 g) and (3S*,4S*)-3-azido-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (312 mg).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux overnight
  3. custompartitioned between ethyl acetate and water
  4. washThe combined organic layers were washed with brine
  5. customseparated
  6. dry with materialdried (MgSO4)
  7. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-80d4bbf2a9d34690ba567607138b9d89
Source dataset
uspto-grants-2012_10
Patent number
US08293735B2

Reaction notes

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