Hydrochloric Acid → 1-[1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazol-4-yl]-3-(2-chloro-phenyl)-propane-1,3-dione

HRID 2251986

Reaktionsgleichung

Reaktionsgleichung von HRID 2251986
C([N-]C(C)C)(C)C.[Li+].[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16](=[O:18])[CH3:17].CON(C)[C:22]([C:24]1[N:25]=[N:26][N:27]([CH2:35][C:36]2[CH:41]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:39]=[C:38]([C:46]([F:49])([F:48])[F:47])[CH:37]=2)[C:28]=1[C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1)=[O:23].Cl>C1COCC1>[F:45][C:42]([F:43])([F:44])[C:40]1[CH:41]=[C:36]([CH:37]=[C:38]([C:46]([F:47])([F:49])[F:48])[CH:39]=1)[CH2:35][N:27]1[C:28]([C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)=[C:24]([C:22](=[O:23])[CH2:17][C:16]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[Cl:9])=[O:18])[N:25]=[N:26]1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 72864Ethanone, 1-(2-chlorophenyl)-HCID 2724682Lithium diisopropylamideHCID 86601237HCID 86601237, Verbindung

Produkt 1

HCID 866012491-[1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazol-4-yl]-3-(2-chloro-phenyl)-propane-1,3-dioneAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Add lithium diisopropylamide (6 mL, 1.0 M in THF) to a solution of 1-(2-chloro-phenyl)-ethanone (0.929 g, 6.01 mmol) in THF (10 mL) at −78° C. and stir for 30 min. To the above enolate solution at −78° C., add a solution of 1-(3,5-bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid methoxy-N-methyl-amide (1.29 g, 2.81 mmol) in THF (15 mL) via cannula. Warm solution to 70° C. and stir for 4 hours, than add 1N HCl (6 mL) and stir for an additional 30 min. Concentrate the mixture in vacuo to ¼ volume, dilute with EtOAc (60 mL) and wash with water (30 mL), saturated NaHCO3 (30 mL), and brine (30 mL). Dry, filter, and concentrate the organic phase and purify the crude material by flash chromatography using a linear gradient of 20% to 80% EtOAc/hexanes to give the title compound (1.07 g, 69%) as an orange foam. MS (IS) 553.2 (M+1), MS (ES−) 551.2 (M−1). 1H NMR (400 MHz, CDCl3): δ 15.5 (m, 1H), 7.78 (dd, 1H, J=1.3, 4.8), 8.54 (d, 1H, J=2.2), 7.81 (s, 1H), 7.64 (dd, 1H, J=2.0, 7.7), 7.57 (dt, 1H, J=2.0, 7.9), 7.44 (m, 4H), 7.38 (dt, 1H, J=1.8, 7.5), 7.33 (dt, 1H, J=1.5, 7.5), 7.19 (s, 1H), 5.59 (s, 2H).

Aufarbeitung

  1. stirringWarm solution to 70° C. and stir for 4 hours
  2. stirringstir for an additional 30 min
  3. concentrationConcentrate the mixture in vacuo
  4. additiondilute with EtOAc (60 mL)
  5. washwash with water (30 mL), saturated NaHCO3 (30 mL), and brine (30 mL)
  6. customDry
  7. filtrationfilter
  8. concentrationconcentrate the organic phase
  9. custompurify the crude material by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-5d45546754bb42fcb64387fa4583a837
Quelldatensatz
uspto-grants-2008_01
Patentnummer
US07320994B2

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