Hydrochloric Acid → JNJ17156516

HRID 2376257Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2376257
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[N:12]=[C:11]([CH2:22][C@@H:23]([C:39]3[CH:40]=[C:41]([CH3:45])[CH:42]=[CH:43][CH:44]=3)[C:24](N3[C@H]4C5C=CC=CC=5C[C@H]4OC3=O)=[O:25])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[OH:46]O.[Li+].[OH-].Cl>O.C1COCC1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=3)[N:12]=[C:11]([CH2:22][C@@H:23]([C:39]3[CH:40]=[C:41]([CH3:45])[CH:42]=[CH:43][CH:44]=3)[C:24]([OH:46])=[O:25])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 58630661HCID 58630661, Verbindung

Produkt 1

HCID 11488979JNJ17156516

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 22635083Tetrahydrofuran tolueneLösungsmittel

Reaktionsbedingungen

Temperatur
5 °C

Versuchsvorschrift

To a stirred THF/toluene solution containing 3-{3-[5-(3,4-dichlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionyl}-3,3a,8,8a-tetrahydro-indeno[1,2-d]oxazol-2-one (Example 520, 9.45 kg, 14.8 mol) at 0-10° C. was added H2O (5.25 L) and 30% hydrogen peroxide (4.35 L, 42.6 mol) followed by 19% aq. LiOH (9.40, 42.6 mol). The reaction mixture was stirred between 0-10° C. for 2 h. When HPLC analysis indicated the disappearance of the starting material, the reaction was quenched between 0-10° C. with 1.5 N sodium meta-bisulfite solution (8.0 L) maintaining the pH at 9-10. The quenched reaction mixture was then acidified to pH 1-2 using 6 N HCl (8.4 L). After removing the aqueous layer, ˜60.0 L of the organic phase was removed under reduced pressure, and EtOAc (8.5 L) was added. The resultant suspension was filtered and washed. The filtrate, containing the desired acid, was used directly in the next synthetic step without isolation. Chemical characterization data obtained herein for the title compound is not duplicated in this Example in light of the same data given in Example 1, Step H.

Aufarbeitung

  1. customthe reaction was quenched between 0-10° C. with 1.5 N sodium meta-bisulfite solution (8.0 L)
  2. temperaturemaintaining the pH at 9-10
  3. customThe quenched reaction mixture
  4. customAfter removing the aqueous layer, ˜60.0 L of the organic phase
  5. customwas removed under reduced pressure, and EtOAc (8.5 L)
  6. additionwas added
  7. filtrationThe resultant suspension was filtered
  8. washwashed
  9. additionThe filtrate, containing the desired acid

Quellen und Nachweise

ORD-Eintrag
ord-d9de0ba5d13f47fc88eca383818ae195
Quelldatensatz
uspto-grants-2008_12
Patentnummer
US07465808B2

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