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

HRID 61493Notes

Reaction equation

HRID 61493 reaction equation
[O:1]=[C:2]1[CH2:7][C@H:6]([C:8]([O:10][CH3:11])=[O:9])[C@@H:5]([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=[O:13])[CH2:4][CH2:3]1.[C:26]1([Mg]Br)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCCC1>[OH:1][C:2]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:7][C@H:6]([C:8]([O:10][CH3:11])=[O:9])[C@@H:5]([C:12]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:16][CH2:15]2)=[O:13])[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 67304345Methyl (1s,2s)-5-oxo-2-[(4-phenylpiperazin-1-yl)carbonyl]cyclohexanecarboxylateHCID 178418255HCID 178418255, compound

Product 1

HCID 67304499Methyl(1s,2s)-5-hydroxy-5-phenyl-2-[(4-phenylpiperazin-1-yl)carbonyl]-cyclohexanecarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of methyl(1S,2S)-5-oxo-2-[(4-phenylpiperazin-1-yl)carbonyl]-cyclohexanecarboxylate (130.0 mg, 0.0003775 mol) in anhydrous tetrahydrofuran (4.0 mL, 0.049 mol) at −78° C. was added 1.00 M of phenylmagnesium bromide in tetrahydrofuran (0.755 mL). The reaction mixture was stirred at −78° C. for 1 h, then slowly warmed to −35° C. over 3 h. The reaction was quenched with saturated aqueous NH4Cl (20 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 30-80% EtOAc/Hex to give the product as a colorless solid. (123 mg, 62% in yield). MS (ESI): (M+H)+=423.1.

Workup

  1. temperatureslowly warmed to −35° C. over 3 h
  2. customThe reaction was quenched with saturated aqueous NH4Cl (20 mL)
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by Combiflash with 30-80% EtOAc/Hex

Sources & evidence

ORD record
ord-88c4268bb514425cb51f0385f569712c
Source dataset
uspto-grants-2016_09
Patent number
US09440958B2

Reaction notes

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