Reaktion #45542

Reaktionsgleichung

pivaloyl chloride

pyridine

benzene

2-amino-4-bromo-5-iodo-3-methoxy-6-methylbenzoic acid

→

7-bromo-2-tert-butyl-6-iodo-8-methoxy-5-methylbenzo[d][1,3]oxazin-4-one

Ausbeute 97.3%

Lösungsmittel

ethyl acetate

toluene

Ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenthe organic layer was washed with 1 N hydrochloric acid (30 ml×2), saturated brine (30 ml×2)
2. 2
   Trocknendried over anhydrous magnesium sulfate
3. 3
   Einengenconcentrated under reduced pressure
4. 4
   workup.ADDITIONTo the residue, added
5. 5
   workup.STIRRINGby stirring at room temperature for 15 minutes
6. 6
   workup.STIRRINGstirring at 50° C. for 1.15 hours
7. 7
   Temperaturby refluxing for 30 minutes
8. 8
   TemperaturAfter cooling
9. 9
   Waschenthe organic layer was washed with 1 N hydrochloric acid (30 ml×2), saturated brine (30 ml×2)
10. 10
    Trocknendried over anhydrous magnesium sulfate
11. 11
    Einengenconcentrated under reduced pressure

Vorschrift

A benzene (1.0 ml) suspension of 2-amino-4-bromo-5-iodo-3-methoxy-6-methylbenzoic acid (I-4) (77 mg, 199 μmol) was cooled at 0° C., pivaloyl chloride (61.4 μl, 499 μmol), pyridine (40.3 μl, 499 μmol) were put thereinto, followed by stirring at room temperature for 1 hour. Ethyl acetate (30 ml) was added to the reaction liquid, the organic layer was washed with 1 N hydrochloric acid (30 ml×2), saturated brine (30 ml×2), then dried over anhydrous magnesium sulfate, concentrated under reduced pressure. To the residue, added were toluene (2.0 ml), 4-dimethylaminopyridine (25.6 mg, 209 μmol), followed by stirring at room temperature for 15 minutes and then stirring at 50° C. for 1.15 hours, further followed by refluxing for 30 minutes. After cooling, ethyl acetate (30 ml) was added, the organic layer was washed with 1 N hydrochloric acid (30 ml×2), saturated brine (30 ml×2), then dried over anhydrous magnesium sulfate, then concentrated under reduced pressure to obtain 7-bromo-2-tert-butyl-6-iodo-8-methoxy-5-methylbenzo[d][1,3]oxazin-4-one (87.5 mg, 97%) as a yellow ocher solid. A tetrahydrofuran (1.0 ml) solution of a part of it (65 mg, 144 μmol) was cooled at 0° C., followed by adding aqueous 28% ammonia (97.1 μl, 1.44 mmol) and stirring overnight with gradually heating up to room temperature. On the next day, this was further cooled at 0° C., followed by adding aqueous 28% ammonia (97.1 μl, 1.44 mmol) and stirring for 2 hours with gradually heating up to room temperature. Aqueous saturated ammonium chloride solution (30 ml) was added to the reaction liquid, the product was extracted with ethyl acetate (30 ml×2). The organic layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, the residue was purified by silica gel column chromatography (chloroform:ethyl acetate=4:1→chloroform:methanol=20:1) to obtain the entitled compound (35.8 mg, 53%) as a colorless solid.

Quelle