Sodium Carbonate → 2-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aRS)-4-(4-methoxybenzyl)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]ethan-1-one

HRID 1876815Notes

Reaction equation

HRID 1876815 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]=O)=[CH:7][CH:8]=1.[BH3-]C#N.[Na+].[Cl:15][C:16]1[CH:17]=[C:18]([CH2:23][C:24]([N:26]2[CH:35]3[CH:30]([CH2:31][CH2:32][CH2:33][CH:34]3[N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[NH:29][CH2:28][CH2:27]2)=[O:25])[CH:19]=[CH:20][C:21]=1[Cl:22].C([O-])([O-])=O.[Na+].[Na+]>CO.C(O)(=O)C>[Cl:15][C:16]1[CH:17]=[C:18]([CH2:23][C:24]([N:26]2[CH:35]3[CH:30]([CH2:31][CH2:32][CH2:33][CH:34]3[N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[N:29]([CH2:9][C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:28][CH2:27]2)=[O:25])[CH:19]=[CH:20][C:21]=1[Cl:22]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312444-MethoxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 687760732-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aRS)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]-ethan-1-one

Product 1

HCID 687788902-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aRS)-4-(4-methoxybenzyl)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]ethan-1-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

Anisaldehyde (361 mg, 2.6 mmol) was dissolved in 5 ml of MeOH and NaBH3CN (170 mg, 2.6 mmol) was added. The pH was adjusted to 5 with concentrated acetic acid. 2-(3,4-Dichlorophenyl)-1-[(4aRS,8SR,8aRS)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]-ethan-1-one (105 mg, 0.26 mmol), dissolved in MeOH (15 ml), was then added to the mixture and the mixture was stirred overnight. After addition of saturated Na2CO3 solution (15 ml), the mixture was stirred at room temperature for 15 minutes. The precipitate formed was filtered off. The aqueous phase of the filtrate was washed three times with CH2Cl2 and the combined organic phases were dried over Na2SO4 and evaporated in vacuo. The residue was purified by flash chromatography (Ø 2 cm, CH2Cl2/MeOH/NH3 9.5:0.5:0.1, l=15 cm, V=5 ml). The fractions containing the product were evaporated, the residue was taken up in CH2Cl2 and the solution was extracted by shaking three times with HCl (1 N). The aqueous phase was then brought to pH 8 with NaOH (2 N) and extracted by shaking three times with CH2Cl2. The organic phases were dried over Na2SO4 and evaporated in vacuo. A yellowish resin was isolated.

Workup

  1. additionwas then added to the mixture
  2. stirringthe mixture was stirred at room temperature for 15 minutes
  3. customThe precipitate formed
  4. filtrationwas filtered off
  5. washThe aqueous phase of the filtrate was washed three times with CH2Cl2
  6. dry with materialthe combined organic phases were dried over Na2SO4
  7. customevaporated in vacuo
  8. customThe residue was purified by flash chromatography (Ø 2 cm, CH2Cl2/MeOH/NH3 9.5:0.5:0.1, l=15 cm, V=5 ml)
  9. additionThe fractions containing the product
  10. customwere evaporated
  11. extractionthe solution was extracted
  12. stirringby shaking three times with HCl (1 N)
  13. extractionextracted
  14. stirringby shaking three times with CH2Cl2
  15. dry with materialThe organic phases were dried over Na2SO4
  16. customevaporated in vacuo
  17. customA yellowish resin was isolated

Sources & evidence

ORD record
ord-686ea6f351594699bba0aca76314c7c6
Source dataset
uspto-grants-2012_11
Patent number
US08309725B2

Reaction notes

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