Hydrochloric Acid → 4-Cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxamide

HRID 17488Notes

Reaction equation

HRID 17488 reaction equation
C[Al](C)C.CCCCCC.[Cl-].[NH4+:12].[C:13]([C:15]1[C:20]2[N:21]=[C:22]([C:24]([O:26]CC)=O)[O:23][C:19]=2[C:18]([F:29])=[C:17]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:16]=1[CH3:36])#[N:14].Cl>O.ClCCl>[C:13]([C:15]1[C:20]2[N:21]=[C:22]([C:24]([NH2:12])=[O:26])[O:23][C:19]=2[C:18]([F:29])=[C:17]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:16]=1[CH3:36])#[N:14]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 16682925TrimethylaluminumHCID 51041426Ethyl 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxylate

Product 1

HCID 685844314-Cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxamideYield 80.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

At room temperature, trimethylaluminium (4.49 ml, 4.63 mmol, 1.03 M hexane solution was added to an anhydrous dichloromethane (6 ml) suspension of ammonium chloride (247 mg, 4.62 mmol), followed by stirring at room temperature for 20 minutes. A dichloromethane (4 ml) solution of ethyl 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxylate (I-111) (500 mg, 1.54 mmol) was added, followed by stirring for 4 hours and by heating under reflux in an oil bath at 45° C. for 48 hours. With cooling with ice, 1 N hydrochloric acid (10 ml) was added to the reaction liquid, then water (20 ml) was added, followed by extraction with chloroform (100 ml×2). The organic layer was washed with saturated brine (100 ml), then dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the resulting residue was purified in slurry with diethyl ether to obtain the entitled compound (368 mg, 80.8%) as a pale yellow solid.

Workup

  1. stirringby stirring for 4 hours
  2. temperatureby heating
  3. temperatureunder reflux in an oil bath at 45° C. for 48 hours
  4. additionwas added to the reaction liquid
  5. extractionfollowed by extraction with chloroform (100 ml×2)
  6. washThe organic layer was washed with saturated brine (100 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customthe resulting residue was purified in slurry with diethyl ether

Sources & evidence

ORD record
ord-1389553018e64917896f5251d6717674
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

Loading…