Acetic Acid → 2-(3,4-dichlorophenyl)-1-{(4aRS,8SR,8aRS)-4-[(pyridin-3-yl)methyl]-8-(pyrrolidin-1-yl)perhydroquinoxalin-1-yl}ethan-1-one

HRID 1876817Notes

Reaction equation

HRID 1876817 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].[CH:27](=O)[C:28]1[CH:33]=[CH:32][CH:31]=[N:30][CH:29]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(=O)C>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]([CH2:27][C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 103713-Pyridinecarboxaldehyde2×HCID 5049666Sodium triacetoxyborohydride2×HCID 687760732-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aRS)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]-ethan-1-one

Product 1

HCID 687756332-(3,4-dichlorophenyl)-1-{(4aRS,8SR,8aRS)-4-[(pyridin-3-yl)methyl]-8-(pyrrolidin-1-yl)perhydroquinoxalin-1-yl}ethan-1-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(3,4-Dichlorophenyl)-1-[(4aRS,8SR,8aRS)-8-(pyrrolidin-1-yl)-perhydroquinoxalin-1-yl]-ethan-1-one (120 mg, 0.30 mmol) was dissolved in absolute CH2Cl2 (10 ml), and nicotinaldehyde (65 mg, 0.61 mmol), NaBH(OAc)3 (128 mg, 0.61 mmol) and glacial acetic acid (36 mg, 0.61 mmol) were added. The mixture was stirred at room temperature. After 21 hours, the same amounts of nicotinaldehyde, NaBH(OAc)3 and glacial acetic acid were again added and the mixture was stirred for 3.5 hours. The mixture was then filtered and the organic phase was extracted by shaking three times with HCl (1 N). The aqueous phase was 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. The residue was purified by preparative HPLC (as described under Example 14 in MeOH/H2O/Et2NH 80:20:0.1). MeOH was evaporated off from the product fraction, the aqueous phase was extracted by shaking three times with CH2Cl2 and the combined organic phases were dried over Na2SO4 and evaporated. A yellowish resin was isolated.

Workup

  1. stirringthe mixture was stirred for 3.5 hours
  2. filtrationThe mixture was then filtered
  3. extractionthe organic phase was extracted
  4. stirringby shaking three times with HCl (1 N)
  5. extractionextracted
  6. stirringby shaking three times with CH2Cl2
  7. dry with materialThe organic phases were dried over Na2SO4
  8. customevaporated in vacuo
  9. customThe residue was purified by preparative HPLC (as described under Example 14 in MeOH/H2O/Et2NH 80:20:0.1)
  10. customMeOH was evaporated off from the product fraction
  11. extractionthe aqueous phase was extracted
  12. stirringby shaking three times with CH2Cl2
  13. dry with materialthe combined organic phases were dried over Na2SO4
  14. customevaporated
  15. customA yellowish resin was isolated

Sources & evidence

ORD record
ord-4228383178a444b8a25732eacea9394a
Source dataset
uspto-grants-2012_11
Patent number
US08309725B2

Reaction notes

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