Benzyl Chloride → 3-Fluoro-4,5-bis(phenylmethoxy)benzeneacetonitrile

HRID 649087Notes

Reaction equation

HRID 649087 reaction equation
[CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:9][C:10]1[CH:11]=[C:12]([CH:16]=[C:17]([F:20])[C:18]=1O)[CH2:13][C:14]#[N:15].[C:21]([O-:24])([O-])=O.[K+].[K+]>>[CH2:1]([O:9][C:10]1[CH:11]=[C:12]([CH:16]=[C:17]([F:20])[C:18]=1[O:24][CH2:21][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:13][C:14]#[N:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 7503Benzyl ChlorideHCID 11430Potassium CarbonateHCID 13720703(3-Fluoro-4,5-dihydroxyphenyl)acetonitrile

Product 1

HCID 137207043-Fluoro-4,5-bis(phenylmethoxy)benzeneacetonitrileYield 80%

Procedure

Benzyl chloride (0.54 mL), 4.5 mmol) was added to a solution of 3,4-dihydroxy-5-fluorobenzylcyanide 16 (330 mg, 2 mmol), K2CO3 (620 mg, 4.5 mmol) and KI (50 mg) in DMK (10 mL). The mixture was heated at reflux for 4 h, cooled and concentrated under reduced pressure. The residue was dissolved in H2O (10 mL), and EtOAc (10 mL). The organic layer was washed with brine (2×10 mL), H2O (2×10 mL), dried with anhydrous MgSO4 and concentrated under reduced pressure to an oil. The oil was purified by flash chromatography (20% EtOAc/hexanes) to give an oil which solidified on standing. The solid was crystallized from CH2Cl2 /hexanes to give 555 mg (80%) of 12 as white needles: mp 120°-121° C.; IR (KBr) 2400 cm-1 ; 1H NMR (CDCl3) δ 7.47-7.25 (m, 10H, ArH), 6.76-6.61 (m, 2H, ArH), 5.11 (s, 4H, ArCH2), 3.63 (s, 2H, ArCH2CN); analysis calc. for C22H18FNO2 ; C, H, N.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 4 h
  3. temperaturecooled
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in H2O (10 mL)
  6. washThe organic layer was washed with brine (2×10 mL), H2O (2×10 mL)
  7. dry with materialdried with anhydrous MgSO4
  8. concentrationconcentrated under reduced pressure to an oil
  9. customThe oil was purified by flash chromatography (20% EtOAc/hexanes)
  10. customto give an oil which
  11. customThe solid was crystallized from CH2Cl2 /hexanes

Sources & evidence

ORD record
ord-da8f695248a9477cbe968e6476be7911
Source dataset
uspto-grants-1988_04
Patent number
US04737504

Reaction notes

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