Potassium Carbonate → 2'-(Benzyloxy)-2-[4-(tert-butoxycarbonyl)piperazin-1-yl]-4'-fluoroacetophenone

HRID 1433150Notes

Reaction equation

HRID 1433150 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]([O:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C:29](=[O:32])[CH2:30]Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:14]([O:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C:29](=[O:32])[CH2:30][N:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 579348132'-(Benzyloxy)2-bromo4'-fluoroacetophenone

Product 1

HCID 690593352'-(Benzyloxy)-2-[4-(tert-butoxycarbonyl)piperazin-1-yl]-4'-fluoroacetophenoneYield 80.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(tert-Butoxycarbonyl)piperazine (808 mg, 4.34 mmol) was added to a mixture of 2′-(benzyloxy)-2-bromo4′-fluoroacetophenone (assumed 4.13 mmol) and potassium carbonate (856 mg, 6.20 mmol) in DMF, and stirred for 18 h at room temperature. The solvent was removed in vacuo, the residue taken up in ethyl acetate (150 mL) and washed with water (100 mL) and brine (100 mL). The organice layer was dried (MgSO4) and the solvents removed in vacuo. The crude product was purified by flash chromatography, eluting with 9:1 hexane:EtOAc followed by 1:1 hexane:EtOAc to give pure 2′-(benzyloxy)-2-[4-(tert-butoxycarbonyl)piperazin-1-yl]-4′-fluoroacetophenone (1.42 g, 80% over 2 steps) as a yellow oil; Rf 0.00 (9:1 hexane:EtOAc), 0.50 (1:1 hexane:EtOAc); δH (CDCl3) 7.89 (1H, dd, J=9.3 and 6.9 Hz), 7.48-7.44 (5H, m), 6.81-6.77 (2H, m), 5.17 (2H, s), 3.79 (2H, s), 3.51-3.47 (4H, m), 2.44-2.41 (4H, m), 1.50 (9H, s); LCMS retention time 2.10 min, M+H+ 429.4.

Workup

  1. customThe solvent was removed in vacuo
  2. washwashed with water (100 mL) and brine (100 mL)
  3. dry with materialThe organice layer was dried (MgSO4)
  4. customthe solvents removed in vacuo
  5. customThe crude product was purified by flash chromatography
  6. washeluting with 9:1 hexane

Sources & evidence

ORD record
ord-f03db8d5639144f7af01926186f81cb1
Source dataset
uspto-grants-2009_11
Patent number
US07612201B2

Reaction notes

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