Reaktion #70999

Reaktionsgleichung

sodium chlorite

1-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde

sodium phosphate monobasic

2-Methyl-2-butene

→

desired product

1-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid

Lösungsmittel

THF

water

tert-butanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeat 0° C
2. 2
   SonstigeThe ice bath was removed
3. 3
   SonstigeAfter a few minutes the desired product began precipitating out of solution
4. 4
   workup.STIRRINGStirring
5. 5
   workup.ADDITION20 mL of 1N aqueous HCl was added
6. 6
   workup.STIRRINGstirring
7. 7
   workup.WAITwas continued for another 5 minutes
8. 8
   FiltrationThe desired product was filtered off
9. 9
   Waschenwashed with water, ethyl acetate, and ether
10. 10
    Sonstigethe layers were separated
11. 11
    ExtraktionThe aqueous layer was extracted with ethyl acetate
12. 12
    TrocknenThe combined organic layers were dried over magnesium sulfate
13. 13
    Filtrationfiltered
14. 14
    Einengenconcentrated in vacuo
15. 15
    Filtrationfiltered
16. 16
    Waschenwashed with ethyl acetate and ether

Vorschrift

1-(4-Fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carbaldehyde (10.0 g, 29.2 mmol) and sodium phosphate monobasic (10.1 g, 73 mmol, Aldrich) were stirred vigorously in 35 mL each of THF, tert-butanol, and water at 0° C. 2-Methyl-2-butene (45.2 mL, 2.0 M in THF, Aldrich) was added to the reaction mixture, followed by sodium chlorite (6.06 g, 67.1 mmol, Aldrich). The ice bath was removed and the reaction mixture was warmed to room temperature, stirring very rapidly. After a few minutes the desired product began precipitating out of solution. Stirring was continued for 1 h, then 20 mL of 1N aqueous HCl was added, and stirring was continued for another 5 minutes. The desired product was filtered off, then washed with water, ethyl acetate, and ether. The filtrate was taken and the layers were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was suspended in ethyl acetate, filtered, and washed with ethyl acetate and ether to yield additional desired product. The pale yellow solids were combined to yield 8.22 g (78%) of 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid (92% pure, 8% starting material remaining). This material was dissolved in a minimal amount of 1N aqueous NaOH. Ethyl acetate was added and the mixture was stirred vigorously for 5 minutes. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The aqueous layer was acidified, with stirring, using concentrated HCl to pH 1. The pale yellow solid that precipitated out of solution was collected, washed with water, ethyl acetate, diethyl ether and then dried under vacuum to afford 7.33 g (70%) of 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid (95.4% pure by HPLC). 1H NMR (DMSO-d6) δ 13.53 (s, 1H), 7.52-7.49 (m, 3H), 7.38 (t, 2H, J=8.8 Hz), 6.81 (d, 1H, J=7.2 Hz); MS(ESI+) m/z 360.14 (M+H)+.

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