Benzene → HCID 68584499, compound

HRID 17264Notes

Reaction equation

HRID 17264 reaction equation
C1C=CC=CC=1.[NH2:7][C:8]1[C:16]([O:17][CH3:18])=[C:15]([Br:19])[C:14]([I:20])=[C:13]([CH3:21])[C:9]=1[C:10]([OH:12])=[O:11].[C:22](Cl)(=O)[C:23]([CH3:26])([CH3:25])[CH3:24].N1C=CC=CC=1>CN(C)C1C=CN=CC=1.C(OCC)(=O)C.C1(C)C=CC=CC=1>[Br:19][C:15]1[C:14]([I:20])=[C:13]([CH3:21])[C:9]2[C:10](=[O:12])[O:11][C:22]([C:23]([CH3:26])([CH3:25])[CH3:24])=[N:7][C:8]=2[C:16]=1[O:17][CH3:18]

Participants

8

Reactant 4

HCID 241BenzeneHCID 1049PyridineHCID 62493Pivaloyl chlorideHCID 860974752-Amino-4-bromo-5-iodo-3-methoxy-6-methylbenzoic Acid

Product 1

HCID 68584499HCID 68584499, compoundYield 97.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  1. washthe organic layer was washed with 1 N hydrochloric acid (30 ml×2), saturated brine (30 ml×2)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. additionTo the residue, added
  5. stirringby stirring at room temperature for 15 minutes
  6. stirringstirring at 50° C. for 1.15 hours
  7. temperatureby refluxing for 30 minutes
  8. temperatureAfter cooling
  9. washthe organic layer was washed with 1 N hydrochloric acid (30 ml×2), saturated brine (30 ml×2)
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f99e8e302a5f4c57af7d9907597b376b
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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