HCID 59568648, compound → HCID 59568649, compound

HRID 1474350Notes

Reaction equation

HRID 1474350 reaction equation
[C:1]([C:3]1[C:4]([O:25][CH3:26])=[CH:5][C:6]([CH:9]([OH:24])[CH2:10][N:11]2[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)=[N:7][CH:8]=1)#[N:2]>C(O)(C(F)(F)F)=O>[OH:24][CH:9]([C:6]1[N:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([O:25][CH3:26])[CH:5]=1)[CH2:10][N:11]1[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]1

Participants

3

Reactant 1

HCID 59568648HCID 59568648, compound2×

Product 1

HCID 59568649HCID 59568649, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent2×

Procedure

Enantiomer A of tert-Butyl 4-[2-(5-cyano-4-methoxy-2-pyridyl)-2-hydroxy-ethyl]piperazine-1-carboxylate (1.30 g, 3.59 mmol) was dissolved in 5 mL of TFA and stirred at room temperature for 2 h. The mixture was concentrated to ¼ the original volume and diluted with 10 mL of diethyl ether. The precipitate was filtered and dried under high vacuum to offer amine TFA salt. This intermediate was diluted with 5% aqueous sodium bicarbonate with follow up addition of 10 N NaOH to bring the pH of extraction above 10. The aqueous layer was extracted with ethyl acetate. The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to provide the product. LC/MS: (IE, m/z) tR=0.39 min; [M+1]+=263.12 Enantiomer B of tert-Butyl 4-[2-(5-cyano-4-methoxy-2-pyridyl)-2-hydroxy-ethyl]piperazine-1-carboxylate (1.0 g, 2.76 mmol) was dissolved in 5 mL of TFA and stirred at room temperature for 2 h. The mixture was concentrated to ¼ the original volume and diluted with 10 mL of diethyl ether. The precipitate was filtered and dried under high vacuum to offer amine TFA salt. This intermediate was diluted with 5% aqueous sodium bicarbonate with follow up addition of 10 N NaOH to bring the pH of extraction above 10. The aqueous layer was extracted with ethyl acetate. The organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to provide the product. LC/MS: (IE, m/z) tR=0.62 min; [M+1]+=263.09

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with 10 mL of diethyl ether
  3. filtrationThe precipitate was filtered
  4. customdried under high vacuum
  5. additionThis intermediate was diluted with 5% aqueous sodium bicarbonate
  6. additionwith follow up addition of 10 N NaOH
  7. extractionthe pH of extraction above 10
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. dry with materialThe organic layers were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto provide the product
  13. stirringstirred at room temperature for 2 h
  14. concentrationThe mixture was concentrated
  15. additiondiluted with 10 mL of diethyl ether
  16. filtrationThe precipitate was filtered
  17. customdried under high vacuum
  18. additionThis intermediate was diluted with 5% aqueous sodium bicarbonate
  19. additionwith follow up addition of 10 N NaOH
  20. extractionthe pH of extraction above 10
  21. extractionThe aqueous layer was extracted with ethyl acetate
  22. dry with materialThe organic layers were dried over MgSO4
  23. filtrationfiltered
  24. concentrationconcentrated under reduced pressure
  25. customto provide the product

Sources & evidence

ORD record
ord-9ca9bd8a8f0a4e3087bccda098d19d83
Source dataset
uspto-grants-2015_04
Patent number
US09018211B2

Reaction notes

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