Water → 3-amino-8-(2-oxopyrrolidin-1-yl)-1-(thiophen-3-ylmethyl)-3,4-dihydroquinolin-2(1H)-one

HRID 2070167

Reaction equation

HRID 2070167 reaction equation
S(=O)(=O)(O)O.O.[O:7]=[C:8]1[CH:17]([NH:18]C(=O)C)[CH2:16][C:15]2[C:10](=[C:11]([N:22]3[CH2:26][CH2:25][CH2:24][C:23]3=[O:27])[CH:12]=[CH:13][CH:14]=2)[N:9]1[CH2:28][C:29]1[CH:33]=[CH:32][S:31][CH:30]=1.[OH-].[Na+]>C(OCC)(=O)C>[NH2:18][CH:17]1[CH2:16][C:15]2[C:10](=[C:11]([N:22]3[CH2:26][CH2:25][CH2:24][C:23]3=[O:27])[CH:12]=[CH:13][CH:14]=2)[N:9]([CH2:28][C:29]2[CH:33]=[CH:32][S:31][CH:30]=2)[C:8]1=[O:7]

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 14798Sodium Hydroxide2×HCID 59620372N-(2-oxo-8-(2-oxopyrrolidin-1-yl)-1-(thiophen-3-ylmethyl)-1,2,3,4-tetrahydroquinolin-3-yl)acetamide

Product 1

HCID 596203303-amino-8-(2-oxopyrrolidin-1-yl)-1-(thiophen-3-ylmethyl)-3,4-dihydroquinolin-2(1H)-oneYield 77.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
86 °C

Procedure

Sulfuric acid (470.6 mL) was added to water (5.65 L) at room temperature, and N-(2-oxo-8-(2-oxopyrrolidin-1-yl)-1-(thiophen-3-ylmethyl)-1,2,3,4-tetrahydroquinolin-3-yl)acetamide (561.5 g) was added thereto at an internal temperature of 41-43° C. The mixture was heated at an internal temperature of 80 to 92° C. for four hours while being stirred. Under cooling on ice, 25% sodium hydroxide (2,715 g) was added dropwise to the reaction mixture at an internal temperature of 50° C. or lower, to thereby adjust the pH of the mixture to 7. Ethyl acetate (1.0 L) was added to the resultant mixture while being stirred, and 25% sodium hydroxide (300 g) was added thereto at an internal temperature of 50° C. or lower, to thereby adjust the pH of the mixture to 10. An additional ethyl acetate (1.83 L) was added to the mixture, and stirring was performed for five minutes, to thereby partition the mixture. Ethyl acetate (2.83 L) was added to the aqueous layer at an internal temperature of 30° C. or lower, and stirring was performed for five minutes, to thereby partition the mixture. An additional ethyl acetate (2.83 L) was added to the aqueous layer, and the above-described extraction procedure was repeated. The ethyl acetate layers were combined, and the combined ethyl acetate layer was concentrated under reduced pressure, to thereby evaporate ethyl acetate (6.8 L). The reaction mixture was left to stand overnight in a refrigerator, and the crystals that precipitated were recovered through filtration. The thus-recovered crystals were washed with ethyl acetate (566 mL). The thus-obtained solid was dried in air overnight and then at 60° C. under reduced pressure, whereby the title compound (389.2 g) was yielded as pale yellow crystals.

Workup

  1. customat an internal temperature of 41-43° C
  2. additionwas added dropwise to the reaction mixture at an internal temperature of 50° C.
  3. stirringwhile being stirred
  4. customat an internal temperature of 50° C.
  5. stirringstirring
  6. customto thereby partition the mixture
  7. additionEthyl acetate (2.83 L) was added to the aqueous layer at an internal temperature of 30° C.
  8. stirringlower, and stirring
  9. waitwas performed for five minutes
  10. customto thereby partition the mixture
  11. additionAn additional ethyl acetate (2.83 L) was added to the aqueous layer
  12. extractionthe above-described extraction procedure
  13. concentrationthe combined ethyl acetate layer was concentrated under reduced pressure
  14. waitThe reaction mixture was left
  15. waitto stand overnight in a refrigerator
  16. customthe crystals that precipitated
  17. filtrationwere recovered through filtration
  18. washThe thus-recovered crystals were washed with ethyl acetate (566 mL)
  19. customThe thus-obtained solid was dried in air overnight

Sources & evidence

ORD record
ord-311f5725ae894ddca72bbe5be99e5615
Source dataset
uspto-grants-2012_10
Patent number
US08299255B2

Linked notes

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