Water → HCID 68539805, compound

HRID 1445714Notes

Reaction equation

HRID 1445714 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH:14]=[C:13]2[C@@H:8]([CH2:9][C:10]3[C:11]4[C:18]([NH:19][CH:20]=3)=[CH:17][CH:16]=[CH:15][C:12]=42)[N:7](C#N)[CH2:6]1)=[O:4].O>C(O)(=O)C.CO.C(Cl)Cl.[Zn]>[CH3:1][O:2][C:3]([C@@H:5]1[CH:14]=[C:13]2[C@@H:8]([CH2:9][C:10]3[C:11]4[C:18]([NH:19][CH:20]=3)=[CH:17][CH:16]=[CH:15][C:12]=42)[NH:7][CH2:6]1)=[O:4]

Participants

6

Reactant 2

HCID 962WaterHCID 86626151HCID 86626151, compound

Product 1

HCID 68539805HCID 68539805, compound

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a 100 ml round-bottom flask containing a solution of (6aR,9R)-7-Cyano-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid methyl ester (1.57 g, 5.35 mmol) in acetic acid (20 ml) is added water (4 ml) and zinc (1.5 g). The reaction mixture is refluxed at 100° C. for 3 hours by which time TLC in 20% methanol/DCM showed conversion of starting material to give product as a mixture of diastereomers. The reaction mixture is filtered to remove the zinc and the filter paper is washed thoroughly with water (200 ml) and ethyl acetate (200 ml). The aqueous phase is made basic with the addition of solid sodium hydrogen carbonate. The phases are then extracted and allowed to separate. The aqueous phase is re-extracted with ethyl acetate (2×100 ml) and the combined organic phases washed with brine (200 ml), dried (MgSO4), filtered at the pump and concentrated in vacuo to give a beige coloured foam. Purification is carried out by Normal Phase Flash column chromatography (Biotage Flash 40, 40 g cartridge) using 10% methanol/dichloromethane to achieve separation. Product is isolated as a beige foam.

Workup

  1. customto give product
  2. additionas a mixture of diastereomers
  3. filtrationThe reaction mixture is filtered
  4. customto remove the zinc
  5. washthe filter paper is washed thoroughly with water (200 ml) and ethyl acetate (200 ml)
  6. additionThe aqueous phase is made basic with the addition of solid sodium hydrogen carbonate
  7. extractionThe phases are then extracted
  8. customto separate
  9. extractionThe aqueous phase is re-extracted with ethyl acetate (2×100 ml)
  10. washthe combined organic phases washed with brine (200 ml)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered at the pump
  13. concentrationconcentrated in vacuo
  14. customto give
  15. customPurification
  16. customseparation
  17. customProduct is isolated as a beige foam

Sources & evidence

ORD record
ord-0e0fe3faffbf4f2bb27d86e532c064d8
Source dataset
uspto-grants-2010_02
Patent number
US07666877B2

Reaction notes

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