Sodium Carbonate → Piperazin-1-yl-acetic acid

HRID 1989869Notes

Reaction equation

HRID 1989869 reaction equation
[N:1]1([C:7]2C=CC(NC(C3C(C4C=CC(C(F)(F)F)=CC=4)=CC=CC=3)=O)=CC=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:32]([O-:35])([O-])=[O:33].[Na+].[Na+].BrC(C1C=CC=CC=1)C(OC)=O>CN(C=O)C>[N:1]1([CH2:7][C:32]([OH:35])=[O:33])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 137806Benzeneacetic acid, alpha-bromo-, methyl esterHCID 112010994'-Trifluoromethyl-biphenyl-2-carboxylic acid [4-(piperazinyl)-phenyl]-amide

Product 1

HCID 650402Piperazin-1-yl-acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of intermediate (2) (0.019 mol) and Na2CO3 (0.019 mol) in DMF (125 ml) was stirred. Methyl 2-bromo-2-phenylacetate (0.019 mol) was added dropwise. The mixture was stirred at room temperature for 3 hours. The solvent was evaporated. The residue was stirred in DCM and washed with water. The separated organic layer was dried, filtered and the solvent was evaporated. The residue was stirred in DIPE. The precipitate was filtered off, dried and separated by high performance liquid chromatography over Chiralcel OD (eluent:hexane/EtOH 70/30) in its enantiomers. The desired fractions were collected and the solvent was evaporated, yielding 1-piperazineacetic acid, α-phenyl-4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-, methyl ester, (α1A)-(intermediate 33) after crystallisation from 2-propanol, and 1-piperazineacetic acid, α-phenyl-4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-, methyl ester, (α1B)-(intermediate 34) after crystallisation from 2-propanol.

Workup

  1. stirringThe mixture was stirred at room temperature for 3 hours
  2. customThe solvent was evaporated
  3. stirringThe residue was stirred in DCM
  4. washwashed with water
  5. customThe separated organic layer was dried
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. stirringThe residue was stirred in DIPE
  9. filtrationThe precipitate was filtered off
  10. customdried
  11. customseparated by high performance liquid chromatography over Chiralcel OD (eluent:hexane/EtOH 70/30) in its enantiomers
  12. customThe desired fractions were collected
  13. customthe solvent was evaporated

Sources & evidence

ORD record
ord-50c12dc9a67540a9adf5845cea21e4cf
Source dataset
uspto-grants-2010_01
Patent number
US07642378B2

Reaction notes

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