Acetic Acid → Tert-butyl 4-(4-amino-3-fluorophenyl)piperazine-1-carboxylate

HRID 1503838Notes

Reaction equation

HRID 1503838 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O.C(O)(=O)C>[Zn].O1CCCC1.CO>[NH2:8][C:7]1[CH:6]=[CH:5][C:4]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:13][CH2:12]2)=[CH:3][C:2]=1[F:1]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 66738172Tert-butyl 4-(3-fluoro-4-nitrophenyl)piperazine-1-carboxylate

Product 1

HCID 57652076Tert-butyl 4-(4-amino-3-fluorophenyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixture of the product of Example 28A (1.6 g, 4.9 mmol), zinc dust (3.2 g, 49 mmol) and acetic acid (5.4 mL) in 1/1 tetrahydrofuran/methanol (100 mL) was stirred at ambient temperature for 1 hour. The mixture was filtered and the filtrate was diluted with water and adjusted to pH 9. The mixture was extracted with ethyl acetate and the combined organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (200-300 mesh) eluting with 99/1 dichloromethane/methanol to give the title compound. MS: 296 (M+H+).

Workup

  1. filtrationThe mixture was filtered
  2. additionthe filtrate was diluted with water
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe combined organic phase was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography on silica gel (200-300 mesh)
  9. washeluting with 99/1 dichloromethane/methanol

Sources & evidence

ORD record
ord-f86f30308d844574881c63cbdf09ac61
Source dataset
uspto-grants-2015_12
Patent number
US09212192B2

Reaction notes

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