Sodium Hydroxide → AZD 8329

HRID 1160508Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1160508
[OH-].[Na+].[CH:3]12[CH2:12][CH:7]3[CH2:8][CH:9]([CH2:11][CH:5]([CH2:6]3)[CH:4]1[NH:13][C:14]([C:16]1[CH:17]=[N:18][N:19]([C:25]3[CH:34]=[CH:33][C:28]([C:29]([O:31]C)=[O:30])=[CH:27][CH:26]=3)[C:20]=1[C:21]([CH3:24])([CH3:23])[CH3:22])=[O:15])[CH2:10]2>CO>[CH:3]12[CH2:10][CH:9]3[CH2:8][CH:7]([CH2:6][CH:5]([CH2:11]3)[CH:4]1[NH:13][C:14]([C:16]1[CH:17]=[N:18][N:19]([C:25]3[CH:34]=[CH:33][C:28]([C:29]([OH:31])=[O:30])=[CH:27][CH:26]=3)[C:20]=1[C:21]([CH3:23])([CH3:24])[CH3:22])=[O:15])[CH2:12]2

Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 59516081HCID 59516081, Verbindung

Produkt 1

HCID 25006684AZD 8329Ausbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
62.5 °C

Versuchsvorschrift

Aqueous sodium hydroxide (2M) (2.5 eq) was added portionwise over 5 minutes to a stirred suspension of methyl 4-[4-(2-adamantylcarbamoyl)-5-tert-butyl-pyrazol-1-yl]benzoate (Intermediate#56) (1.0 eq) in methanol (10 vol) at 20° C. (exotherm 20-27° C.). The resulting suspension was heated to 70° C. (jacket temperature), (batch refluxes approx 60-65° C.) for 1 hour (complete by LCMS). The orange reaction mixture was cooled to 20° C. (solution remained slightly cloudy) and filtered through celite to remove a small amount of solids. The filtrate was then poured into a flange flask and water (25 vol) was added. The mixture was then adjusted to pH 3 with 2M HCl (approx 800-850 ml) (turns very thick). The aqueous was then filtered and the pale yellow solid washed with water, sucked dry overnight, and washed with acetonitrile and finally 1:1 acetonotrile/diethyl ether and dried under vacuum at 50° C. for 72 hours (weekend) to give 4-[4-(2-adamantylcarbamoyl)-5-tertbutyl-pyrazol-1-yl]benzoic acid (80%) as a solid.

Aufarbeitung

  1. temperatureThe orange reaction mixture was cooled to 20° C. (solution
  2. filtrationfiltered through celite
  3. customto remove a small amount of solids
  4. additionThe filtrate was then poured into a flange flask
  5. additionwater (25 vol) was added
  6. filtrationThe aqueous was then filtered
  7. washthe pale yellow solid washed with water
  8. customsucked dry overnight
  9. washwashed with acetonitrile and finally 1:1 acetonotrile/diethyl ether
  10. customdried under vacuum at 50° C. for 72 hours (weekend)

Quellen und Nachweise

ORD-Eintrag
ord-f35d7423daa642e29b9e7e6caefd37d2
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07816391B2

Notizen zur Reaktion

Wird geladen…