Citric Acid → 8-[(Tert-butoxy)carbonyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid

HRID 341486Notes

Reaction equation

HRID 341486 reaction equation
[C:1]([O:5][C:6]([N:8]1C2CCC1CC(C#N)C2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].[CH3:20][CH2:21]O.[C:23](O)(=O)[CH2:24][C:25]([CH2:30][C:31](O)=O)([C:27]([OH:29])=[O:28])O>O>[C:1]([O:5][C:6]([N:8]1[CH:23]2[CH2:20][CH2:21][CH:31]1[CH2:30][CH:25]([C:27]([OH:29])=[O:28])[CH2:24]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 702EthanolHCID 14797Potassium HydroxideHCID 53487658tert-Butyl 3-cyano-8-azabicyclo[3.2.1]octane-8-carboxylate2×

Product 1

HCID 185070258-[(Tert-butoxy)carbonyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 3-cyano-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (Intermediate 104, 190 mg, 0.81 mmol) was added potassium hydroxide (270 mg, 4.83 mmol), EtOH (3 mL) and water (1 mL). The mixture was heated at 95 C for 4 h, allowed to cool and acidified to pH=2 with a 1 M aq. solution of citric acid. The mixture was then extracted with EtOAc (2×5 mL) and the combined extracts washed with saturated brine (10 mL), and dried over anhydrous sodium sulfate. Evaporation gave the crude title compound which was used directly without further purification (190 mg, 94%). Method B HPLC-MS: MH+ requires m/z=255. Found: m/z=200 (MH-tBu), Rt=1.68 min (76%).

Workup

  1. temperatureThe mixture was heated at 95 C for 4 h
  2. temperatureto cool
  3. extractionThe mixture was then extracted with EtOAc (2×5 mL)
  4. washthe combined extracts washed with saturated brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customEvaporation

Sources & evidence

ORD record
ord-be631896be96422a95d0c6ee4bbe344a
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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