Dimethylformamide → Methyl (1s,2s)-5-oxo-2-[(4-phenylpiperazin-1-yl)carbonyl]cyclohexanecarboxylate

HRID 61488Notes

Reaction equation

HRID 61488 reaction equation
[CH3:1][O:2][C:3]([C@H:5]1[CH2:10][C:9](=[O:11])[CH2:8][CH2:7][C@@H:6]1[C:12]([OH:14])=O)=[O:4].CN(C)C=O.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.[C:53]1([N:59]2[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]2)[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1.C(N(CC)C(C)C)(C)C>>[O:11]=[C:9]1[CH2:10][C@H:5]([C:3]([O:2][CH3:1])=[O:4])[C@@H:6]([C:12]([N:62]2[CH2:63][CH2:64][N:59]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[CH2:60][CH2:61]2)=[O:14])[CH2:7][CH2:8]1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 70961-PhenylpiperazineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 67304222(1s,2s)-2-(Methoxycarbonyl)-4-oxocyclohexanecarboxylic acid

Product 1

HCID 67304345Methyl (1s,2s)-5-oxo-2-[(4-phenylpiperazin-1-yl)carbonyl]cyclohexanecarboxylateYield 74.5%

Procedure

To a stirred solution of (1S,2S)-2-(methoxycarbonyl)-4-oxocyclohexanecarboxylic acid (1.014 g, 0.005065 mol) in anhydrous N,N-dimethylformamide (20.0 mL, 0.258 mol) at rt was added (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (2.989 g, 0.005572 mol), 1-phenylpiperazine (1.17 mL, 0.00760 mol), followed by N,N-diisopropylethylamine (2.66 mL, 0.0152 mol). The reaction mixture was stirred at rt for 15 h. The reaction was quenched with water (40 mL), extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by Combiflash with 40-70% EtOAc/Hex. to give the product as a colorless solid (1.299 g, 74% in yield). MS (ESI): (M+H)+=345.1.

Workup

  1. customThe reaction was quenched with water (40 mL)
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by Combiflash with 40-70% EtOAc/Hex

Sources & evidence

ORD record
ord-5c661e6a97fe40459a21f48f1391f69b
Source dataset
uspto-grants-2016_09
Patent number
US09440958B2

Reaction notes

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