Sodium Hydroxide → Trans 4-(2-Chloro-4-fluoro-phenoxy)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 1714403Notes

Reaction equation

HRID 1714403 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C@@H:12]2[C@@H:10]([O:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[OH:23].[OH-].[Na+].[Cl-].[NH4+]>O1CCOCC1.CCCCCCC.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C@@H:12]([O:23][C:17]2[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=2[Cl:15])[C@H:10]([OH:11])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 748142-Chloro-4-fluorophenolHCID 55273474tert-butyl (1S,6R)-7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate

Product 1

HCID 68506255Trans 4-(2-Chloro-4-fluoro-phenoxy)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21899848Ethylacetate heptaneSolvent2×

Procedure

Rac-cis-7-Oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (1 g, 5 mmol) was solvated in dioxane (5 mL), 2-Chloro-4-Fluorophenol was added (1.471 g, 10 mmol) and sodium hydroxide (0.401 g, 10 mmol). After 20 hours refluxing, the mixture was cooled, ammonium chloride was added and the mixture extracted three times with ethyl acetate. The combined organic phases were dried with magnesium sulfate and concentrated under vacuum. After a flash chromatography with heptane/ethyl acetate 1:1 to 1:2 heptane/ethyl acetate a solid the title compound was obtained as solid (0.778 g, 45% yield). MS (m/e): 404.5 (M+AcO−).

Workup

  1. temperatureAfter 20 hours refluxing
  2. temperaturethe mixture was cooled
  3. extractionthe mixture extracted three times with ethyl acetate
  4. dry with materialThe combined organic phases were dried with magnesium sulfate
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-0f043f77be3f4268a079654f59e3fdfa
Source dataset
uspto-grants-2010_09
Patent number
US07795437B2

Reaction notes

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