Toluene → 7-Fluoro-2-(methoxymethyl)-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17313Notes

Reaction equation

HRID 17313 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1.[CH3:20][O:21][CH2:22][C:23]([O:25][C:26]1[C:27]([F:42])=[C:28]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:29]([CH3:35])=[C:30]([C:33]#[N:34])[C:31]=1[NH2:32])=O>C(OCC)(=O)C>[F:42][C:27]1[C:28]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[C:29]([CH3:35])[C:30]([C:33]#[N:34])=[C:31]2[C:26]=1[O:25][C:23]([CH2:22][O:21][CH3:20])=[N:32]2

Participants

5

Reactant 3

HCID 1140TolueneHCID 521998p-Toluenesulfonic acid monohydrateHCID 866308254-Amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl methoxyacetate

Product 1

HCID 685851157-Fluoro-2-(methoxymethyl)-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileYield 79.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

p-Toluenesulfonic acid monohydrate (38 mg, 0.2 mmol) was added to a toluene (30 ml) solution of 4-amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl methoxyacetate (I-58) (214 mg, 0.68 mmol), followed by stirring for 3 hours and a half with heating under reflux. After cooling to room temperature, the reaction liquid was diluted with ethyl acetate, washed with saturated sodium bicarbonate water and saturated brine, then dried over anhydrous magnesium sulfate. After filtration and concentration under reduced pressure, the resulting residue was subjected to column chromatography, and the eluate with n-hexane:ethyl acetate (4:1) was concentrated under reduced pressure to obtain the entitled compound (160 mg, 79%) as a pale yellow solid.

Workup

  1. temperaturea half with heating
  2. temperatureunder reflux
  3. customthe reaction liquid
  4. washwashed with saturated sodium bicarbonate water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationAfter filtration and concentration under reduced pressure
  7. concentrationthe eluate with n-hexane:ethyl acetate (4:1) was concentrated under reduced pressure

Sources & evidence

ORD record
ord-433faaa8360747c4866bfea78d305049
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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