Sodium hydride → HCID 68158804, Verbindung

HRID 514219

Reaktionsgleichung

Reaktionsgleichung von HRID 514219
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])(OCC)=O)C.[F:19][C:20]([F:42])([F:41])[O:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH:32]=[N:31][C:30]([C:33]3[CH:40]=[CH:39][C:36]([CH:37]=O)=[CH:35][CH:34]=3)=[N:29]2)=[CH:24][CH:23]=1.[Cl-].[NH4+]>C1COCC1>[C:15]([O:14][C:12](=[O:13])/[CH:11]=[CH:37]/[C:36]1[CH:39]=[CH:40][C:33]([C:30]2[N:31]=[CH:32][N:28]([C:25]3[CH:26]=[CH:27][C:22]([O:21][C:20]([F:41])([F:19])[F:42])=[CH:23][CH:24]=3)[N:29]=2)=[CH:34][CH:35]=1)([CH3:16])([CH3:17])[CH3:18]

Komponenten

6

Edukt 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2773685tert-Butyl diethylphosphonoacetateHCID 578244624-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde

Produkt 1

HCID 68158804HCID 68158804, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sodium hydride (NaH, 60% suspension in mineral oil; 440 milligrams (mg), 11.0 millimoles (mmol)) was suspended in THF (20 milliliters (mL)), and the mixture was cooled to 0° C. t-Butyl diethylphosphonoacetate (2.57 mL; 11.0 mmol) was added over 2 minutes (min). The mixture was stirred at 0° C. for another 15 min, during which time the grey slurry turned clear within 5 min. 4-[1-(4-Trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde (3.04 grams (g); 9.13 mmol) was suspended in THF (20 mL) and then added dropwise via cannula to the solution above. The mixture was then warmed to 25° C., poured into saturated (satd) aqueous (aq) ammonium chloride (NH4Cl; 200 mL), and extracted with 50% ethyl acetate (EtOAc)/hexanes (3×100 mL). The combined organic extracts were then dried over sodium sulfate (Na2SO4) and concentrated in vacuo. The yellow solid residue was dissolved in dichloromethane (CH2Cl2; 10 mL) and rapidly stirred as hexanes (100 mL) was added dropwise over 30 min. The light yellow crystals were collected on a Büchner funnel and dried in vacuo to afford the title compound ((2.93 g, 74%). The filtrate was concentrated in vacuo and purified by chromatography on silica gel (gradient elution with 15% to 40% to 80% EtOAc in hexanes) to afford additional product (0.215 g, 5%): mp 167-169° C.; 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 8.20 (d, J=8.3 Hz, 2H), 7.80 (d, J=8.9 Hz, 2H), 7.63 (d, J=15.8 Hz, 1H), 7.62 (d, J=8.5 Hz, 2H), 7.39 (d, J=8.6 Hz, 2H), 6.44 (d, J=16.0 Hz, 1H), 1.54 (s, 9H); HRMS-ESI (m/z) [M]+ calcd for C22H20F3N3O3, 431.146; found, 431.1457.

Aufarbeitung

  1. additionwas added over 2 minutes (min)
  2. waitturned clear within 5 min
  3. additionadded dropwise via cannula to the solution above
  4. temperatureThe mixture was then warmed to 25° C.
  5. extractionextracted with 50% ethyl acetate (EtOAc)/hexanes (3×100 mL)
  6. dry with materialThe combined organic extracts were then dried over sodium sulfate (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. dissolutionThe yellow solid residue was dissolved in dichloromethane (CH2Cl2; 10 mL)
  9. stirringrapidly stirred as hexanes (100 mL)
  10. additionwas added dropwise over 30 min
  11. customThe light yellow crystals were collected on a Büchner funnel
  12. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-5297ab28d29c48399dce8ad0327a7b0e
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09107410B2

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