Water → HCID 71765150, compound

HRID 2272985Notes

Reaction equation

HRID 2272985 reaction equation
C([O:3][C:4]([C:6]1[N:7]([CH2:12][C:13](=O)[C:14]2[CH:19]=[CH:18][C:17]([CH:20]3[CH2:25][CH2:24][N:23](C(=O)C(F)(F)F)[CH2:22][CH2:21]3)=[CH:16][CH:15]=2)[CH:8]=[C:9]([F:11])[CH:10]=1)=O)C.C([O-])(=O)C.[NH4+:37].O>C(O)(=O)C>[F:11][C:9]1[CH:10]=[C:6]2[C:4](=[O:3])[NH:37][C:13]([C:14]3[CH:15]=[CH:16][C:17]([CH:20]4[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]4)=[CH:18][CH:19]=3)=[CH:12][N:7]2[CH:8]=1

Participants

5

Reactant 3

HCID 962WaterHCID 517165Ammonium AcetateHCID 89826032HCID 89826032, compound

Product 1

HCID 71765150HCID 71765150, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
110 °C

Procedure

4-Fluoro-1-(2-oxo-2-{4-[1-(2,2,2-trifluoro-acetyl)-piperidin-4-yl]-phenyl}-ethyl)-1H-pyrrole-2-carboxylic acid ethyl ester (1.57 g; 3.42 mmol) is dissolved in acetic acid (10 ml) and ammonium acetate (5.80 g; 75.25 mmol) is added. The reaction mixture is stirred at 110° C. overnight. The reaction mixture is allowed to cool to room temperature, poured into cold water (250 ml) and extracted with ethyl acetate. The organic layers are discarded. The aqueous layer is basified with 2N NaOH (pH11). A precipitate forms. The solid is filtered off by suction, washed with water and a small amount of ethyl acetate. Then the solid is dissolved in 150 ml ethyl acetate, dried over Na2SO4, filtered off by suction and evaporated to dryness. The residue is triturated with diethylether, filtered off and dried under vacuum at 50° C. (overnight). The aqueous filtrate is extracted 3 times with ethyl acetate/MeOH (5%). The combined organic layers are washed with brine, dried over Na2SO4, filtered off and evaporated to dryness. The residue is triturated with diethylether, filtered off by suction and dried under vacuum to afford 7-fluoro-3-(4-piperidin-4-yl-phenyl)-2H-pyrrolo[1,2-a]pyrazin-1-one as beige solid; HPLC/MS 1.37 min (A), [M+H] 312;

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with ethyl acetate
  3. filtrationThe solid is filtered off by suction
  4. washwashed with water
  5. dissolutionThen the solid is dissolved in 150 ml ethyl acetate
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered off by suction
  8. customevaporated to dryness
  9. customThe residue is triturated with diethylether
  10. filtrationfiltered off
  11. customdried under vacuum at 50° C. (overnight)
  12. extractionThe aqueous filtrate is extracted 3 times with ethyl acetate/MeOH (5%)
  13. washThe combined organic layers are washed with brine
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered off
  16. customevaporated to dryness
  17. customThe residue is triturated with diethylether
  18. filtrationfiltered off by suction
  19. customdried under vacuum

Sources & evidence

ORD record
ord-7f7d72c4d1d04dd3a070fc1fc357730c
Source dataset
uspto-grants-2015_09
Patent number
US09120805B2

Reaction notes

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