Citric Acid → tert-Butyl (1R,3S,4S,6S)-3-{[(2S)-2-cyano-1-pyrrolidinyl]carbonyl}-6-hydroxy-2-azabicyclo[2.2.1]heptane-2-carboxylate

HRID 456756Notes

Reaction equation

HRID 456756 reaction equation
[C:1]([C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([C@@H:10]1[C@H:15]2[CH2:16][C@H:12]([C:13](=[O:17])[CH2:14]2)[N:11]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:9])#[N:2].[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[C:1]([C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C:8]([C@@H:10]1[C@H:15]2[CH2:16][C@H:12]([C@@H:13]([OH:17])[CH2:14]2)[N:11]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:9])#[N:2]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 4311764Sodium borohydrideHCID 86598907tert-Butyl (1R,3S,4S)-3-{[(2S)-2-cyano-1-pyrrolidinyl]carbonyl}-6-oxo-2-azabicyclo[2.2.1]heptane-2-carboxylate

Product 1

HCID 86598908tert-Butyl (1R,3S,4S,6S)-3-{[(2S)-2-cyano-1-pyrrolidinyl]carbonyl}-6-hydroxy-2-azabicyclo[2.2.1]heptane-2-carboxylateYield 101.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl (1R,3S,4S)-3-{[(2S)-2-cyano-1-pyrrolidinyl]carbonyl}-6-oxo-2-azabicyclo[2.2.1]heptane-2-carboxylate obtained in Example 22-1 (80 mg) in methanol (8 mL), was added sodium borohydride (1 mg). The mixture was stirred at 0° C. for 1 hr. To the reaction mixture, was added citric acid solution. The mixture was extracted with ethyl acetate. The combined organic phase was washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue was triturated with ether to give the target compound (82 mg) as a solid.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washThe combined organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated in vacuo
  5. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-907e8e50039a433e87f4b9e7df54670e
Source dataset
uspto-grants-2007_03
Patent number
US07186731B2

Reaction notes

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