Potassium Carbonate → 4'-Acetamido-2'-benzyloxy-2-[4-(benzyloxycarbonyl)piperazin-1-yl]acetophenone

HRID 1433156Notes

Reaction equation

HRID 1433156 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:17]([O:24][C:25]1[CH:26]=[C:27]([NH:35][C:36](=[O:38])[CH3:37])[CH:28]=[CH:29][C:30]=1[C:31](=[O:34])[CH2:32]Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:36]([NH:35][C:27]1[CH:28]=[CH:29][C:30]([C:31](=[O:34])[CH2:32][N:14]2[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])[CH2:12][CH2:13]2)=[C:25]([O:24][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:26]=1)(=[O:38])[CH3:37]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 643495Benzyl piperazine-1-carboxylateHCID 85606679N-[3-benzyloxy-4-(2-bromo-acetyl)phenyl]-acetamide

Product 1

HCID 690575444'-Acetamido-2'-benzyloxy-2-[4-(benzyloxycarbonyl)piperazin-1-yl]acetophenoneYield 41.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(Benzyloxycarbonyl)piperazine (117 μL, 134 mg, 0.607 mmol) was added to a mixture of N-[3-benzyloxy-4-(2-bromo-acetyl)phenyl]-acetamide (200 mg, 0.552 mmol) and potassium carbonate (115 mg, 0.828 mmol) in DMF (5 mL), and stirred at room temperature for 18 hours. The solvent was removed in vacuo, and taken up in brine (25 mL). The aqueous was extracted with DCM (3×25 mL) and the combined organics dried (MgSO4). The solvents were removed in vacuo, and the product was purified by preparative HPLC to give pure 4′-acetamido-2′-benzyloxy-2-[4-(benzyloxycarbonyl)piperazin-1-yl]acetophenone (114 mg, 41%, 50% rec.) as an off-white solid; δH (CDCl3) 8.23 (1H, br s), 7.81 (1H, d, J=8.6 Hz), 7.77-7.76 (1H, m), 7.53-7.51 (2H, m), 7.42-7.28 (8H, m), 7.08 (1H, dd, J=8.6, 1.8 Hz), 5.20 (2H, s), 5.12 (2H, s), 4.00 (2H, s), 3.59-3.48 (4H, m), 2.65-2.60 (4H, m), 2.14 (3H, s); LCMS retention time 2.07 min, M+H+ 502.5, along with recovered N-(4-acetyl-3-benzyloxy-phenyl)-acetamide (35 mg).

Workup

  1. customThe solvent was removed in vacuo
  2. extractionThe aqueous was extracted with DCM (3×25 mL)
  3. dry with materialthe combined organics dried (MgSO4)
  4. customThe solvents were removed in vacuo
  5. customthe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-563f8ad0daf74a0eb68aadd7d6a69792
Source dataset
uspto-grants-2009_11
Patent number
US07612201B2

Reaction notes

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