Toluene → Benzyl 2-(4-cyano-7-fluoro-5-methyl-6-phenylbenzoxazol-2-yl)-2-methylpropionate

HRID 17316Notes

Reaction equation

HRID 17316 reaction equation
[CH3:1][C:2]([CH3:26])([C:23]([O-:25])=[O:24])[C:3]([O:5][C:6]1[C:7]([F:22])=[C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:9]([CH3:15])=[C:10]([C:13]#[N:14])[C:11]=1[NH2:12])=O.O.[C:28]1([CH3:38])[CH:33]=[CH:32][C:31](S(O)(=O)=O)=[CH:30][CH:29]=1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[C:13]([C:10]1[C:11]2[N:12]=[C:3]([C:2]([CH3:26])([CH3:1])[C:23]([O:25][CH2:38][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:24])[O:5][C:6]=2[C:7]([F:22])=[C:8]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:9]=1[CH3:15])#[N:14]

Participants

5

Reactant 3

HCID 1140TolueneHCID 521998p-Toluenesulfonic acid monohydrateHCID 866308264-Amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl 2,2-dimethylmalonate

Product 1

HCID 68585926Benzyl 2-(4-cyano-7-fluoro-5-methyl-6-phenylbenzoxazol-2-yl)-2-methylpropionateYield 856.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl 2,2-dimethylmalonate (I-63) (500 mg, 1.12 mmol), p-toluenesulfonic acid monohydrate (21 mg, 0.112 mmol) and toluene (20 ml) was heated under reflux for 2 hours. After cooling, the reaction liquid was diluted with ethyl acetate, successively washed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine, dried on anhydrous magnesium sulfate, then the solvent was evaporated away to obtain a pale brown residue. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1) to obtain the entitled compound (411 mg, 86%) as a colorless solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 hours
  3. temperatureAfter cooling
  4. customthe reaction liquid
  5. washsuccessively washed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine
  6. dry with materialdried on anhydrous magnesium sulfate
  7. customthe solvent was evaporated away
  8. customto obtain a pale brown residue
  9. customThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1)

Sources & evidence

ORD record
ord-01f59e144b3a4bffbcc0a62b2f70e8c6
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

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