Reaktion #949268

Reaktionsgleichung

2-bromo-4-chloro-5-fluorophenol methoxymethylether

diethyl ether

n-butyllithium hexane

2-cyano-3-trimethylsilyloxypyridine

→

2-(5-chloro-4-fluoro-2-methoxymethoxybenzoyl)-3-hydroxypyridine

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONTo the solution was added dropwise, under argon atmosphere
2. 2
   SonstigeThe cooling bath was then removed
3. 3
   workup.STIRRINGthe reaction mixture was stirred overnight
4. 4
   workup.ADDITIONThe reaction was suspended by the addition of methanol (50 ml)
5. 5
   workup.DISTILLATIONThen the solvent was distilled off
6. 6
   workup.ADDITIONTo the residue were added methanol (300 ml) and conc. hydrochloric acid (7 ml)
7. 7
   workup.STIRRINGThe mixture was stirred for 2 hours at room temperature
8. 8
   Extraktionwas subjected to extraction with ethyl acetate
9. 9
   TrocknenThe extract solution was dried (anhydrous magnesium sulfate)
10. 10
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure
11. 11
    SonstigeThe residue was purified by means of a silica gel column chromatography (elution with ethyl acetate/hexane)

Vorschrift

A solution of 2-bromo-4-chloro-5-fluorophenol methoxymethylether (17.65 g) in diethyl ether (400 ml) was cooled to -78° C. To the solution was added dropwise, under argon atmosphere, 1.6M n-butyllithium hexane solution (45 ml). The mixture was stirred for one hour under the same conditions, followed by dropwise addition of 2-cyano-3-trimethylsilyloxypyridine (13.18 g) at -78° C. The cooling bath was then removed, and the reaction mixture was stirred overnight while raising the temperature to room temperature. The reaction was suspended by the addition of methanol (50 ml). Then the solvent was distilled off. To the residue were added methanol (300 ml) and conc. hydrochloric acid (7 ml). The mixture was stirred for 2 hours at room temperature. The reaction mixture was neutralized with an aqueous solution of potassium carbonate, which was subjected to extraction with ethyl acetate. The extract solution was dried (anhydrous magnesium sulfate), then the solvent was distilled off under reduced pressure. The residue was purified by means of a silica gel column chromatography (elution with ethyl acetate/hexane) to afford 2-(5-chloro-4-fluoro-2-methoxymethoxybenzoyl)-3-hydroxypyridine (9.18 g) (Compound F-1). Physico-chemical properties and spectrum data are shown in Table 22 and Table 23.

Quelle