2-Chloro-N-(4-fluoro-2-phenylaminophenyl)acetamide → 2-(chloromethyl)-6-fluoro-1-phenyl-1H-1,3-benzodiazole

HRID 243003Notes

Reaction equation

HRID 243003 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=O>CC(O)=O>[Cl:1][CH2:2][C:3]1[N:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:7]2[CH:8]=[C:9]([F:12])[CH:10]=[CH:11][C:6]=2[N:5]=1

Participants

3

Reactant 1

HCID 681579372-Chloro-N-(4-fluoro-2-phenylaminophenyl)acetamide

Product 1

HCID 623773732-(chloromethyl)-6-fluoro-1-phenyl-1H-1,3-benzodiazole

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-chloro-N-(4-fluoro-2-phenylaminophenyl)acetamide (740 mg, 2.62 mmol) in AcOH (20 mL) was heated at 70° C. for 5 h under a nitrogen atmosphere. The volatiles were removed in vacuo and the resulting residue partitioned between DCM and a saturated aqueous solution of NaHCO3. The aqueous phase was further extracted with DCM (×3) and the combined organic fractions washed with water, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM) to afford the title compound as a brown oil which crystallised on standing (570 mg, 84%). LCMS (Method C): RT 3.40 min [M+H]+ 261.2.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe resulting residue partitioned between DCM
  3. extractionThe aqueous phase was further extracted with DCM (×3)
  4. washthe combined organic fractions washed with water
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-0a10d22115e44b4482951560c4a0ecaa
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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