Reaktion #515754

Reaktionsgleichung

sodium hydroxide

methanesulfonic acid

amide acetal

N-(2,2-Dimethoxyethyl)-4-iodobenzamide

phosphorus pentoxide

hydrochloric acid

methyl methanesulfonate

→

title compound

2-(4-Iodophenyl) oxazole

Lösungsmittel

tetrahydrofuran

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled to 0° C.
2. 2
   Temperaturwhile maintaining the reaction temperature below 40° C
3. 3
   Temperaturthe reaction mixture was heated at ca. 45° C.
4. 4
   TemperaturThe reaction mixture was cooled to ambient temperature
5. 5
   Sonstigethe layers were separated
6. 6
   ExtraktionThe spent aqueous phase was extracted twice with 100 mL of acetone
7. 7
   workup.ADDITION200 mL of water was added to effect crystallization
8. 8
   FiltrationThe crystal slurry was filtered
9. 9
   Waschenwashed
10. 10
    Sonstigedried in vacuo at <50° C.

Vorschrift

Under an inert atmosphere, methanesulfonic acid (141 g, 1.46 mol) was added to a mixture of amide acetal (25 g, 74.6 mmol) and phosphorus pentoxide (25 g, 176 mmol). The reaction mixture was heated at 140° C. for about 12 hours. The reaction mixture was cooled to 0° C. and 150 mL of water was added while maintaining the reaction temperature below 40° C. The pH of the reaction mixture was adjusted to 12.5-13 with 50% sodium hydroxide and the reaction mixture was heated at ca. 45° C. to hydrolyze the carcinogenic byproduct methyl methanesulfonate. The reaction mixture was cooled to ambient temperature and 100 mL of tetrahydrofuran was added. The pH was adjusted to 5 with concentrated hydrochloric acid and the layers were separated. The spent aqueous phase was extracted twice with 100 mL of acetone. The rich organic extracts were combined and 200 mL of water was added to effect crystallization. The crystal slurry was filtered, washed and dried in vacuo at <50° C., to give 17 g (84 M %, HPLC area % >99) of the title compound.

Quelle