Sodium hydride → 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-iodonicotinaldehyde

HRID 337277

Reaktionsgleichung

Reaktionsgleichung von HRID 337277
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[NH:10][N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].F[C:20]1[N:27]=[CH:26][CH:25]=[C:24]([I:28])[C:21]=1[CH:22]=[O:23]>C1COCC1>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:20]1[C:21]([CH:22]=[O:23])=[C:24]([I:28])[CH:25]=[CH:26][N:27]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 99923282-Fluoro-4-iodopyridine-3-carbaldehydeHCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-one

Produkt 1

HCID 866737152-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-4-iodonicotinaldehydeAusbeute 70,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

In a 1 L round-bottomed flask, 6-tert-butyl-8-fluorophthalazin-1(2H)-one (5.6 g, 25.4 mmol, Eq: 1.00) was combined with THF (300 ml) to give a colorless solution. Sodium hydride (1.12 g, 28.0 mmol, Eq: 1.1) was added. The reaction mixture was stirred at ambient temperature for 10 min. 2-Fluoro-4-iodonicotinaldehyde (7.02 g, 28.0 mmol, Eq: 1.1) was added and the reaction mixture was stirred at ambient temperature for 1 h. The reaction was complete as determined by LCMS analysis. The reaction mixture was quenched with saturated NH4Cl. The reaction mixture was poured into 200 mL H2O and extracted 3× with CH2Cl2. The organic layers were washed with brine, then dried over Na2SO4 and concentrated in vacuo. The resultant bright yellow solid was transferred into a filter funnel and the flask washed twice with a small volume of EtOAc to ensure complete transfer of the solid into the funnel. The liquid was filtered through. The solid was triturated twice with Et2O and dried under vacuum to afford the desired product as a cream-colored solid (8.09 g, 17.9 mmol, 70.5% yield). (M+H)+=452 m/e. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9 H) 7.49-7.54 (m, 1 H) 7.54 (d, J=1.77 Hz, 1 H) 8.03 (d, J=5.31 Hz, 1 H) 8.30 (d, J=2.53 Hz, 1 H) 8.37 (d, J=5.31 Hz, 1 H) 9.98 (s, 1 H).

Aufarbeitung

  1. customto give a colorless solution
  2. stirringthe reaction mixture was stirred at ambient temperature for 1 h
  3. customThe reaction mixture was quenched with saturated NH4Cl
  4. additionThe reaction mixture was poured into 200 mL H2O
  5. extractionextracted 3× with CH2Cl2
  6. washThe organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe resultant bright yellow solid was transferred into a filter funnel
  10. washthe flask washed twice with a small volume of EtOAc
  11. filtrationThe liquid was filtered through
  12. customThe solid was triturated twice with Et2O
  13. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-6b782cb049df4784b8af59b1437a25a8
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889682B2

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