Hydrochloric Acid → 1-(tert-Butoxycarbonyl)-3-fluoropyrrolidine-3-carboxylic acid

HRID 217455Notes

Reaction equation

HRID 217455 reaction equation
[F:1][C:2]1([C:14]([O:16]C)=[O:15])[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.Cl>CC(O)=O>[C:10]([O:9][C:7]([N:4]1[CH2:5][CH2:6][C:2]([F:1])([C:14]([OH:16])=[O:15])[CH2:3]1)=[O:8])([CH3:13])([CH3:11])[CH3:12]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 595113461-Tert-butyl 3-methyl 3-fluoropyrrolidine-1,3-dicarboxylate

Product 1

HCID 470036011-(tert-Butoxycarbonyl)-3-fluoropyrrolidine-3-carboxylic acidYield 74.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To 1-tert-butyl 3-methyl 3-fluoropyrrolidine-1,3-dicarboxylate (100 mg) was added a mixed solution of concentrated hydrochloric acid (1 mL) and AcOH (0.2 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred for 1 hour, and then stirred at 100° C. for 5 hours. After confirming that the starting materials were lost, the resultant was concentrated under reduced pressure and then azeotroped with toluene three times. The residue was dissolved in a mixed liquid of acetone (0.6 mL) and water (1 mL), and Na2CO3 (64 mg) and DIBOC (132 mg) were added thereto at 0° C., followed by warming to room temperature and then stirring for 15 hours. The reaction mixture was concentrated under reduced pressure and acetone was evaporated. To the residue was added diethylether for liquid separation. The aqueous layer was combined, cooled to 0° C., and adjusted to pH=2 to 3 with 2 M hydrochloric acid. EtOAc was added thereto for extraction. The organic layer was washed with brine, dried over MgSO4, and then concentrated under reduced pressure to obtain 1-(tert-butoxycarbonyl)-3-fluoropyrrolidine-3-carboxylic acid (70 mg) as a white solid.

Workup

  1. stirringstirred at 100° C. for 5 hours
  2. concentrationthe resultant was concentrated under reduced pressure
  3. customazeotroped with toluene three times
  4. dissolutionThe residue was dissolved in a mixed liquid of acetone (0.6 mL) and water (1 mL), and Na2CO3 (64 mg) and DIBOC (132 mg)
  5. additionwere added
  6. customat 0° C.
  7. temperatureby warming to room temperature
  8. stirringstirring for 15 hours
  9. concentrationThe reaction mixture was concentrated under reduced pressure and acetone
  10. customwas evaporated
  11. additionTo the residue was added diethylether
  12. customfor liquid separation
  13. temperaturecooled to 0° C.
  14. additionEtOAc was added
  15. extractionfor extraction
  16. washThe organic layer was washed with brine
  17. dry with materialdried over MgSO4
  18. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-91947d9d3fca44e78197370afb7955c7
Source dataset
uspto-grants-2012_06
Patent number
US08193378B2

Reaction notes

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