4-Cyano-3-fluorobenzyl bromide → Methyl 1-(4-cyano-3-fluorobenzyl)imidazol-5-ylacetate

HRID 2306193Notes

Reaction equation

HRID 2306193 reaction equation
C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:8]2[CH:12]=[C:11]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[N:10]=[CH:9]2)C=CC=CC=1.[C:30]([C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Br)=[CH:34][C:33]=1[F:40])#[N:31]>C(#N)C>[C:30]([C:32]1[CH:39]=[CH:38][C:35]([CH2:36][N:10]2[C:11]([CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:12][N:8]=[CH:9]2)=[CH:34][C:33]=1[F:40])#[N:31]

Participants

4

Reactant 2

HCID 27784664-Cyano-3-fluorobenzyl bromideHCID 105239671-(triphenylmethyl)-1H-Imidazole-4-acetic acid methyl ester

Product 1

HCID 11108504Methyl 1-(4-cyano-3-fluorobenzyl)imidazol-5-ylacetate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl [1-(triphenylmethyl)-1H-imidazol-4-yl]acetate, as described above in Step B, (536 mg, 1.40 mmol) and 4-cyano-3-fluorobenzyl bromide, as described in Example 1, Step D, (300 mg, 1.40 mmol) in acetonitrile (3 mL) was heated to 50° C. for 2 hours. The mixture was allowed to cool, and the solid collected by filtration. The acetonitrile filtrate was concentrated in vacuo to a volume of approximately 1 mL and then reheated to 50° C. for 2 hours, cooled, and the solid removed by filtration. The two crops of precipitated imidazolium salts were combined in MeOH (30 mL) and the solution was heated to reflux for 2 hours, then concentrated in vacuo. The residue was partitioned between saturated aqueous NaHCO3 (20 mL) and CHCl3 (30 mL). The aqueous layer was extracted further with CHCl3 (2×15 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with CHCl3—3% MeOH—0.3% NH4OH to CHCl3—5% MeOH—0.5% NH4OH to yield the titled product as a white solid.

Workup

  1. temperatureto cool
  2. filtrationthe solid collected by filtration
  3. concentrationThe acetonitrile filtrate was concentrated in vacuo to a volume of approximately 1 mL
  4. temperaturecooled
  5. customthe solid removed by filtration
  6. temperaturethe solution was heated
  7. temperatureto reflux for 2 hours
  8. concentrationconcentrated in vacuo
  9. customThe residue was partitioned between saturated aqueous NaHCO3 (20 mL) and CHCl3 (30 mL)
  10. extractionThe aqueous layer was extracted further with CHCl3 (2×15 mL)
  11. dry with materialThe combined organic extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe crude product was purified by flash column chromatography on silica
  15. washeluting with CHCl3—3% MeOH—0.3% NH4OH to CHCl3—5% MeOH—0.5% NH4OH

Sources & evidence

ORD record
ord-01aa18e0bef54d11a63ba3c94eb9cd33
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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