m-Chloroperbenzoic acid → tert-Butyl 4-(2-fluoro-4-hydroxyphenyl)piperazine-1-carboxylate

HRID 271566Notes

Reaction equation

HRID 271566 reaction equation
[F:1][C:2]1[CH:7]=[C:6](C=O)[CH:5]=[CH:4][C:3]=1[N:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1.ClC1C=CC=C(C(OO)=[O:31])C=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([OH:31])[CH:5]=[CH:4][C:3]=1[N:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1

Participants

5

Reactant 3

HCID 70297m-Chloroperbenzoic acid2×HCID 516892Sodium BicarbonateHCID 20785664tert-Butyl 4-(2-fluoro-4-formylphenyl)piperazine-1-carboxylate

Product 1

HCID 20785666tert-Butyl 4-(2-fluoro-4-hydroxyphenyl)piperazine-1-carboxylateYield 29.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-(2-fluoro-4-formyl-phenyl)-piperazine-1-carboxylic acid, tert.-butyl ester (97 mmol) in CH2Cl2 (600 ml), m-chloroperbenzoic acid (194 mmol) is added at 0° C. for 5 min and NaHCO3 (243 mmol) is added at 0° C. The mixture is stirred at 0° C. for 20 min and at room temperature for 1 h. To the mixture, m-chloroperbenzoic acid (48.5 mmol) is added at 0° C. The reaction mixture is stirred at room temperature for 1 h, slowly quenched with saturated NaHCO3 at 0° C. and extracted with AcOEt. The combined extracts are washed with saturated NaHCO3, brine and dried over magnesium sulfate. The solvent is evaporated. To the residue, 10% KOH/EtOH is added at 0° C. and the reaction mixture is stirred at room temperature for 1 h. After the mixture is extracted with AcOEt, the organic layer is washed with brine, dried over magnesium sulfate and filtered. The solvent is evaporated and the residue is chromatographed on silica gel (eluent; n-hexane, n-hexane:AcOEt=5:1, n-hexane:AcOEt=4:1, n-hexane:AcOEt=3:1) to give 8.5 g of desired 4-(2-fluoro-4-hydroxy-phenyl)-piperazine-1-carboxylic acid, tert.-butyl ester.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 1 h
  2. customslowly quenched with saturated NaHCO3 at 0° C.
  3. extractionextracted with AcOEt
  4. washThe combined extracts are washed with saturated NaHCO3, brine
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent is evaporated
  7. additionTo the residue, 10% KOH/EtOH is added at 0° C.
  8. stirringthe reaction mixture is stirred at room temperature for 1 h
  9. extractionAfter the mixture is extracted with AcOEt
  10. washthe organic layer is washed with brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. customThe solvent is evaporated
  14. customthe residue is chromatographed on silica gel (eluent; n-hexane, n-hexane:AcOEt=5:1, n-hexane:AcOEt=4:1, n-hexane:AcOEt=3:1)

Sources & evidence

ORD record
ord-ffa61c2ed9914771aa1ee12a3cd07d10
Source dataset
uspto-grants-2008_11
Patent number
US07452886B2

Reaction notes

Loading…