Hydrochloric Acid → 7-Fluoro-5-methyl-2-(morpholin-4-ylcarbonyl)-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17381

Reaction equation

HRID 17381 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C[Al](C)C.[C:11]([C:13]1[C:18]2[N:19]=[C:20]([C:22](OCC)=[O:23])[O:21][C:17]=2[C:16]([F:27])=[C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:14]=1[CH3:34])#[N:12].Cl>ClCCl>[F:27][C:16]1[C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[C:14]([CH3:34])[C:13]([C:11]#[N:12])=[C:18]2[C:17]=1[O:21][C:20]([C:22]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[O:23])=[N:19]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 16682925TrimethylaluminumHCID 51041426Ethyl 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxylate

Product 1

HCID 685848967-Fluoro-5-methyl-2-(morpholin-4-ylcarbonyl)-6-phenyl-1,3-benzoxazole-4-carbonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Morpholine (269 μl, 3.08 mmol) was dissolved in dichloromethane (3 ml), and under nitrogen atmosphere at room temperature, trimethylaluminium (1.03 M hexane solution, 2.99 ml, 3.08 mmol) was added. After stirring at the same temperature for 15 minutes, a solution of ethyl 4-cyano-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-2-carboxylate (I-111) (500 mg, 1.54 mmol) dissolved in dichloromethane (7 ml) was added at the same temperature. After stirring at the same temperature for 30 hours, an aqueous 1 M hydrochloric acid solution was gradually added at 0° C. The solution was extracted three times with dichloromethane. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away under reduced pressure, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=3:2) to obtain the entitled compound (460 mg, 82%) as a white solid.

Workup

  1. additionwas added at the same temperature
  2. stirringAfter stirring at the same temperature for 30 hours
  3. extractionThe solution was extracted three times with dichloromethane
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe insoluble matter was separated by filtration
  7. customthe solvent was evaporated away under reduced pressure
  8. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=3:2)

Sources & evidence

ORD record
ord-d9f5cb664ce443f6bc84c78e687b2bc6
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Linked notes

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