Toluene → 2-(2-Benzyloxy-1,1-dimethylethyl)-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17317Notes

Reaction equation

HRID 17317 reaction equation
[CH2:1]([O:8][CH2:9][C:10]([CH3:32])([CH3:31])[C:11]([O:13][C:14]1[C:15]([F:30])=[C:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:17]([CH3:23])=[C:18]([C:21]#[N:22])[C:19]=1[NH2:20])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH2:1]([O:8][CH2:9][C:10]([C:11]1[O:13][C:14]2[C:19](=[C:18]([C:21]#[N:22])[C:17]([CH3:23])=[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:15]=2[F:30])[N:20]=1)([CH3:32])[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 521998p-Toluenesulfonic acid monohydrateHCID 866308284-Amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl 3-benzyloxy-2,2-dimethylpropionate

Product 1

HCID 685844612-(2-Benzyloxy-1,1-dimethylethyl)-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileYield 90.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-amino-5-cyano-2-fluoro-6-methylbiphenyl-3-yl 3-benzyloxy-2,2-dimethylpropionate (I-64) (390 mg, 0.902 mmol), p-toluenesulfonic acid monohydrate (17 mg, 0.09 mmol) and toluene (16 ml) was heated under reflux for 3 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=20:1→10:1) to obtain the entitled compound (337 mg, 90%) as a colorless oil.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 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=20:1→10:1)

Sources & evidence

ORD record
ord-3ba1f1fe62e94edc85996691bf2fb474
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

Loading…