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Hydrochloric Acid → (E)-(R)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid ((S)-1-phenyl-ethyl)-amide

HRID 2222669
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2222669
[C:1]1([C@@H:7]([NH:9][C:10](=[O:46])[CH2:11][C@H:12]([O:38][Si](C(C)(C)C)(C)C)[CH2:13][C:14](=[O:37])/[CH:15]=[CH:16]/[C:17]2[C:18]([CH:34]3[CH2:36][CH2:35]3)=[N:19][C:20]3[C:25]([C:26]=2[C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)C.Cl.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.CCCCCC>[C:1]1([C@@H:7]([NH:9][C:10](=[O:46])[CH2:11][C@H:12]([OH:38])[CH2:13][C:14](=[O:37])/[CH:15]=[CH:16]/[C:17]2[C:18]([CH:34]3[CH2:35][CH2:36]3)=[N:19][C:20]3[C:25]([C:26]=2[C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 516892Sodium BicarbonateHCID 11365699(E)-(R)-3-(tert-Butyl-dimethyl-silanyloxy)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-5-oxo-hept-6-enoic acid ((S)-1-phenyl-ethyl)-amide

Produkt 1

HCID 11214592(E)-(R)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid ((S)-1-phenyl-ethyl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8058HexaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
2 °C

Versuchsvorschrift

Crude (E)-(R)-3-(tert-Butyl-dimethyl-silanyloxy)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-5-oxo-hept-6-enoic acid ((S)-1-phenyl-ethyl)-amide (655.1 g) from example c) is placed in a 4-necked, round bottomed flask, equipped with a mechanical stirrer, digital thermometer, nitrogen inlet-outlet and a condenser. Ethanol (2400 mL) is added to obtain a solution. The solution is cooled to 0-4° C. and hydrochloric acid (2M aqueous solution, 657.1 g, 1276 mmol) is added dropwise at this temperature. The reaction mixture is warmed up to 25° C. and stirred at this temperature for additional 4 hours for completion of the deprotection. The reaction mixture is then poured onto an aqueous solution of sodium bicarbonate (7400 mL of a 2% solution) and extracted with ethyl acetate (5000 mL). The organic layer is washed with brine (1800 mL), the water layers are combined and extracted with ethyl acetate (2000 mL). The organic layers are combined, dried over magnesium sulfate and the solvent is evaporated in vacuo to obtain 561.2 g of a braun, honey-like crude product. The crude product is dissolved in toluene (860 mL) and n-hexane (1075 mL) is added. The mixture is heated at 60° C. for 2 hours and at 50° C. for 1 hour. n-Hexane (1075 mL) is added at 50° C. and the suspension is allowed to cool down to room temperature. Stirring is continued over night at room temperature and for additional 3 hours at 0° C. The solid product is isolated by filtration, the filter cake is washed with ice-cold n-hexane (502 mL) and dried in vacuo to obtain (E)-(R)-7-[2-cyclopropyl-4-(4-fluoro-phenyl)-quinolin-3-yl]-3-hydroxy-5-oxo-hept-6-enoic acid ((S)-1-phenyl-ethyl)-amide as a yellow powder.

Aufarbeitung

  1. customequipped with a mechanical stirrer
  2. customto obtain a solution
  3. temperatureThe reaction mixture is warmed up to 25° C.
  4. extractionextracted with ethyl acetate (5000 mL)
  5. washThe organic layer is washed with brine (1800 mL)
  6. extractionextracted with ethyl acetate (2000 mL)
  7. dry with materialdried over magnesium sulfate
  8. customthe solvent is evaporated in vacuo
  9. customto obtain 561.2 g of a braun, honey-like crude product
  10. temperatureThe mixture is heated at 60° C. for 2 hours and at 50° C. for 1 hour
  11. temperatureto cool down to room temperature
  12. stirringStirring
  13. waitis continued over night at room temperature and for additional 3 hours at 0° C
  14. customThe solid product is isolated by filtration
  15. washthe filter cake is washed with ice-cold n-hexane (502 mL)
  16. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-6c6b18d177154dfa85825e8d3309aee1
Quelldatensatz
uspto-grants-2008_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07371865B2

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