Water → Tert-butyl 4-bromo-3-methylphenyl(5-cyano-6-methoxypyridin-2-yl)carbamate

HRID 1260174Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1260174
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][C:3]=1[CH3:16].[H-].[Na+].Cl[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([O:28][CH3:29])[N:21]=1.O>CN(C)C=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([O:28][CH3:29])[N:21]=2)[C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[CH:4][C:3]=1[CH3:16]

Komponenten

6

Edukt 4

HCID 962WaterHCID 24758Sodium hydrideHCID 143811116-Chloro-2-methoxynicotinonitrileHCID 59822380tert-Butyl (4-bromo-3-methylphenyl)carbamate

Produkt 1

HCID 67306440Tert-butyl 4-bromo-3-methylphenyl(5-cyano-6-methoxypyridin-2-yl)carbamateAusbeute 49,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of tert-butyl 4-bromo-3-methylphenylcarbamate (4.36 g, 15.24 mmol) in N,N-dimethylformamide (60 mL) on an ice bath under a nitrogen balloon was added sodium hydride (0.610 g, 15.24 mmol). The reaction was stirred on an ice-water bath for 10 min. The ice bath was removed and to the solution was added a solution of 6-chloro-2-methoxynicotinonitrile (3.85 g, 22.86 mmol) in N,N-dimethylformamide (40 mL) dropwise. After addition completed, the mixture was stirred overnight at 50° C. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain the crude product. The crude was then purified by silica gel column (100% hexanes to 8:2 hexanes/ethyl acetate) to give tert-butyl 4-bromo-3-methylphenyl(5-cyano-6-methoxypyridin-2-yl)carbamate (3.15 g, 49%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.37 (s, 9H), 2.30 (s, 3H), 3.55 (s, 3H), 7.00 (dd, J=2.6, 8.4 Hz, 1H), 7.22 (d, J=2.5 Hz, 1H), 7.40 (d, J=8.5 Hz, 1H), 7.58 (d, J=8.4 Hz, 1H), 8.17 (d, J=8.4 Hz, 1H), 8.30 (d, J=8.0 Hz, 1H).

Aufarbeitung

  1. customThe ice bath was removed and to the solution
  2. additionAfter addition
  3. stirringthe mixture was stirred overnight at 50° C
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried on anhydrous sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto obtain the crude product
  9. customThe crude was then purified by silica gel column (100% hexanes to 8:2 hexanes/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-adef3b708e024e6fbffaefbc0e0e5988
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08470803B2

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