2-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aRS)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]-ethan-1-one → 3-{(4aRS,8SR,8aRS)-1-[2-(3,4-dichlorophenyl)acetyl]-8-(pyrrolidin-1-yl)-perhydroquinoxalin-4-yl}-3-oxopropionic acid

HRID 1876810Notes

Reaction equation

HRID 1876810 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([N:12]2[CH:21]3[CH:16]([CH2:17][CH2:18][CH2:19][CH:20]3[N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[NH:15][CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].[Cl-].C[O:29][C:30](=[O:35])[CH2:31][C:32](O)=[O:33]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([N:12]2[CH:21]3[CH:16]([CH2:17][CH2:18][CH2:19][CH:20]3[N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)[N:15]([C:32](=[O:33])[CH2:31][C:30]([OH:35])=[O:29])[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 687760732-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aRS)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]-ethan-1-oneHCID 86615040Malonic acid methylester chloride

Product 1

HCID 687777193-{(4aRS,8SR,8aRS)-1-[2-(3,4-dichlorophenyl)acetyl]-8-(pyrrolidin-1-yl)-perhydroquinoxalin-4-yl}-3-oxopropionic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under N2, 2-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aRS)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]-ethan-1-one (103 mg, 0.26 mmol) was dissolved in absolute CH2Cl2 (13 ml) and malonic acid monomethyl ester chloride (42 mg, 0.31 mmol) was added dropwise. The mixture was stirred at room temperature overnight and then evaporated in vacuo. The residue was taken up in 20 ml and 2 N NaOH (2 ml) was added. The solution was stirred at room temperature overnight. Thereafter, the mixture was evaporated in vacuo and the residue was purified by flash chromatography (Ø 2 cm, CH2Cl2/MeOH/NH3 8:2:0.1, l=15 cm, V=5 ml). The crude product was taken up in CH2Cl2 again, the mixture was filtered with a glass filter crucible G4 and Celite® (kieselguhr from CELITE Corp., Lompoc, USA) and the filtrate was evaporated in vacuo. A colorless solid was obtained.

Workup

  1. customevaporated in vacuo
  2. additionwas added
  3. stirringThe solution was stirred at room temperature overnight
  4. customThereafter, the mixture was evaporated in vacuo
  5. customthe residue was purified by flash chromatography (Ø 2 cm, CH2Cl2/MeOH/NH3 8:2:0.1, l=15 cm, V=5 ml)
  6. filtrationthe mixture was filtered with a glass
  7. filtrationfilter crucible G4 and Celite® (kieselguhr from CELITE Corp., Lompoc, USA)
  8. customthe filtrate was evaporated in vacuo
  9. customA colorless solid was obtained

Sources & evidence

ORD record
ord-477e0557c2b5436e98273e44f8b0d0ec
Source dataset
uspto-grants-2012_11
Patent number
US08309725B2

Reaction notes

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