2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → (4S,5R)-3-((E)-2-Methyl-hex-2-enoyl)-4,5-diphenyl-oxazolidin-2-one

HRID 132657

Reaktionsgleichung

Reaktionsgleichung von HRID 132657
[C:1]1([C@H:7]2[C@@H:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[O:10][C:9](=[O:18])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19]/[C:20](=[CH:24]\[CH2:25][CH3:26])/[C:21]([OH:23])=O.[CH3:27]COC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1.[Li+].[Cl-]>CCOC(C)=O>[CH3:19]/[C:20](=[CH:24]\[CH2:25][CH2:26][CH3:27])/[C:21]([N:8]1[C@@H:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C@@H:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[O:10][C:9]1=[O:18])=[O:23]

Komponenten

6

Edukt 4

HCID 278332-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinolineHCID 433294Lithium ChlorideHCID 53659092-Methyl-2-pentenoic acidHCID 9859564(4S,5R)-(-)-cis-4,5-Diphenyl-2-oxazolidinone

Produkt 1

HCID 25232302(4S,5R)-3-((E)-2-Methyl-hex-2-enoyl)-4,5-diphenyl-oxazolidin-2-oneAusbeute 94,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A 20 L jacketed reactor was fitted with a reflux condenser. To the reactor was charged 1100 g (4.597 mol) of (4S,5R)-4,5-diphenyl-oxazolidin-2-one, 884 g (6.896 mol) (E)-2-methyl-2-pentenoic acid, 1705 g (6.896 mol) of EEDQ, 48 g (1.149 mol) of LiCl and 16 L of EtOAc. The reaction mixture was heated to 65° C. and was held for 200 minutes. The reaction mixture was cooled to room temperature and was extracted 3× with 3.5 L aliquots of 1N HCl. The combined aqueous extracts were filtered to give a white solid. The recovered white solid was added back to the organic layer. The 20 L reactor was fitted with a distillation head and the organic layer was distilled to remove in succession: 13.5 L of EtOAc, after which 5 L of heptane was added to the reactor; 5 L of EtOAc/heptane, after which 5 L of heptane was added to the reactor; and 2.7 L of EtOAc/heptane, after which 2.7L of heptane was added to the reactor. The contents of the reactor were cooled to 25° C. and the resulting mixture was filtered under 5 psig nitrogen while washing with 4 L of heptane. The wet cake was dried under nitrogen pressure overnight to give 1521 g of the titled compound: 1H NMR (DMSO) 7.12-6.94 (m, 8H), 6.834 (dd, 2H, J=7.813, 1.709), 6.060 (d, 1H, J=8.057), 6.050 (td, 1H, J=7.447, 1.221), 5.795 (d, 1H, J=8.057), 2.119-2.064 (m, 2H), 1.778 (d, 3H, J=0.997), 1.394 (m, 2H), 0.874 (t, 3H, J=7.324); Anal Calc'd for C22H23N1O3: C, 75.62; H, 6.63; N, 4.01. Found: C, 75.26; H, 6.72; N, 3.95.

Aufarbeitung

  1. customwas fitted with a reflux condenser
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionwas extracted 3× with 3.5 L aliquots of 1N HCl
  4. filtrationThe combined aqueous extracts were filtered
  5. customto give a white solid
  6. additionThe recovered white solid was added back to the organic layer
  7. customThe 20 L reactor was fitted with a distillation head
  8. distillationthe organic layer was distilled
  9. customto remove in succession
  10. addition13.5 L of EtOAc, after which 5 L of heptane was added to the reactor
  11. addition5 L of EtOAc/heptane, after which 5 L of heptane was added to the reactor
  12. additionand 2.7 L of EtOAc/heptane, after which 2.7L of heptane was added to the reactor
  13. temperatureThe contents of the reactor were cooled to 25° C.
  14. filtrationthe resulting mixture was filtered under 5 psig nitrogen
  15. washwhile washing with 4 L of heptane
  16. customThe wet cake was dried under nitrogen pressure overnight

Quellen und Nachweise

ORD-Eintrag
ord-f20c2472b45e4e1a81ce578756a69876
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07388023B2

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