4-Cyano-3-fluorobenzyl bromide → HCID 18433550, compound

HRID 2306222Notes

Reaction equation

HRID 2306222 reaction equation
C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[N:8]2[CH:12]=[C:11]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[N:10]=[CH:9]2)C=CC=CC=1.[C:31]([C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Br)=[CH:35][C:34]=1[F:41])#[N:32]>CCOC(C)=O>[C:31]([C:33]1[CH:40]=[CH:39][C:36]([CH2:37][N:10]2[C:11]([CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[CH:12][N:8]=[CH:9]2)=[CH:35][C:34]=1[F:41])#[N:32]

Participants

4

Reactant 2

HCID 27784664-Cyano-3-fluorobenzyl bromideHCID 10475868Methyl 3-(1-Tritylimidazol-4-yl) Propionate

Product 1

HCID 18433550HCID 18433550, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 3-[1-(triphenylmethyl)-1H-imidazol-4-yl]propionate, as described above in Step C, (5.00 g, 12.6 mmol) and 4-cyano-3-fluorobenzyl bromide, as described in Example 1, Step D, (2.70 g, 12.6 mmol) in EtOAc (30 mL) was heated to 50° C. for 5 hours. The mixture was allowed to cool, and the solid collected by filtration. The EtOAc filtrate was concentrated in vacuo to a volume of approximately 15 mL and then reheated to 50° C. for 3 hours, cooled, and the solid removed by filtration. The two crops of precipitated imidazolium salts were combined in MeOH (120 mL) and CHCl3 (200 mL). The aqueous layer was extracted further with CHCl3 (2×100 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 a gradient of CH2Cl2—1% MeOH—0.1% NH4OH to CH2Cl2—5% MeOH—0.5% NH4OH to yield the titled product.

Workup

  1. temperatureto cool
  2. filtrationthe solid collected by filtration
  3. concentrationThe EtOAc filtrate was concentrated in vacuo to a volume of approximately 15 mL
  4. temperaturecooled
  5. customthe solid removed by filtration
  6. extractionThe aqueous layer was extracted further with CHCl3 (2×100 mL)
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash column chromatography on silica
  11. washeluting with a gradient of CH2Cl2—1% MeOH—0.1% NH4OH to CH2Cl2—5% MeOH—0.5% NH4OH

Sources & evidence

ORD record
ord-ec2afaa8ae5a46e9988dcd73b906d12e
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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