Acetic Acid → 1-(3-Bromo-5-fluorophenyl)-4-cyclopropylpiperazine

HRID 1473867Notes

Reaction equation

HRID 1473867 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.C(O[C:18]1(O[Si](C)(C)C)[CH2:20][CH2:19]1)C.C(O)(=O)C>CO.C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([CH:18]3[CH2:20][CH2:19]3)[CH2:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 114709211-(3-Bromo-5-fluorophenyl)piperazine

Product 1

HCID 595880391-(3-Bromo-5-fluorophenyl)-4-cyclopropylpiperazine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To mixture of 1-(3-bromo-5-fluorophenyl)piperazine (2.91 g, 11 mmol) in MeOH (50 mL) was added (1-ethoxycyclopropoxy)trimethylsilane (13.5 mL, 67.2 mmol), acetic acid (6.5 mL, 112 mmol) and NaBCNH4 (1.0 M in THF) (51 mL, 50.4 mmol). The resulting mixture was heated to 70 C overnight and concentrated in vacuuo to give crude residue which was diluted with EtOAc and washed with 1 N NaOH followed by brine. The organic layer was separated, dried with anhydrous MgSO4, filtered and concentrated in vacuuo to give desired 1-(3-bromo-5-fluorophenyl)-4-cyclopropylpiperazine in quantitative yield.

Workup

  1. temperatureThe resulting mixture was heated to 70 C overnight
  2. concentrationconcentrated in vacuuo
  3. customto give crude residue which
  4. washwashed with 1 N NaOH
  5. customThe organic layer was separated
  6. dry with materialdried with anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuuo

Sources & evidence

ORD record
ord-6b5107bd4f23497a8474ba2ed6ece40c
Source dataset
uspto-grants-2015_04
Patent number
US09018205B2

Reaction notes

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