4-Bromo-2-fluoroaniline → 2-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

HRID 15938

Reaktionsgleichung

Reaktionsgleichung von HRID 15938
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8](=[O:11])[N:7]([CH3:12])[C:6]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][C:15]=1[F:21])=[O:4].BrC1C=CC(N)=C(F)C=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].COC(C1C=CC(=O)N(C)C=1Cl)=O>C1COCC1>[Br:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:6]2[N:7]([CH3:12])[C:8](=[O:11])[CH:9]=[CH:10][C:5]=2[C:3]([OH:4])=[O:2])=[C:15]([F:21])[CH:16]=1

Komponenten

6

Edukt 4

HCID 1230504-Bromo-2-fluoroanilineHCID 2733832Lithium HexamethyldisilazideHCID 57442171Methyl 2-chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylateHCID 66673525Methyl 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate

Produkt 1

HCID 576369362-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acidAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

Preparation of 2-(4-bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester: To a solution of 4-bromo-2-fluorophenylamine (0.192 g, 1.01 mmol) in THF (5 mL) at −78° C. under N2 was added lithium bis(trimethylsilyl)amide (1.50 mL, 1.50 mmol, 1 M solution in hexanes) dropwise. The reaction mixture was stirred for one hour at −78° C. 2-Chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid methyl ester (0.202 g, 1.00 mmol) was then added dropwise as a solution in THF (5 mL) and the reaction mixture was stirred for one hour at −78° C. The reaction mixture was quenched by the addition of H2O and the pH was adjusted to pH 7 with saturated NH4Cl and then diluted with EtOAc. The organic layer was separated and washed with saturated NaCl, dried (Na2SO4), and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/EtOAc, 15:1) gave 0.232 g (65%) pure desired product as a white crystalline solid.

Aufarbeitung

  1. stirringthe reaction mixture was stirred for one hour at −78° C
  2. customThe reaction mixture was quenched by the addition of H2O
  3. additiondiluted with EtOAc
  4. customThe organic layer was separated
  5. washwashed with saturated NaCl
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography (methylene chloride/EtOAc, 15:1)

Quellen und Nachweise

ORD-Eintrag
ord-a7bb07a7451d4d20b7ec436a7e36c3c0
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07732616B2

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