3-Bromo-4-(phenylmethoxy)-benzonitrile → HCID 56984010, compound

HRID 1023579Notes

Reaction equation

HRID 1023579 reaction equation
[CH2:1]([Mg]Br)[CH3:2].Br[C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:9]#[N:10]>C1COCC1.[Cl-].[Cl-].[Zn+2]>[CH2:1]([C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:9]#[N:10])[CH3:2]

Participants

5

Reactant 2

HCID 39600183-Bromo-4-(phenylmethoxy)-benzonitrile2×HCID 178418443HCID 178418443, compound

Product 1

HCID 56984010HCID 56984010, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a 1M solution of ethyl magnesium bromide (2 mL, 1.5 equiv), THF (10 mL) was added and the reaction mixture was cooled down to 0° C. A solution of 0.5 M in THF of zinc dichloride (4 mL, 1.5 equiv) was added slowly and the reaction mixture was stirred for 30 min at the same temperature. Pd(tBu3P)2 (102 mg, 0.1 equiv) was added followed by the addition of a solution of 3-bromo-4-[(phenylmethyl)oxy]benzonitrile (Intermediate 110, 576 mg) in THF and the reaction was allowed to reach room temperature. After stirring 30 minutes, some additional Pd(tBu3P)2 was added (51 mg, 0.05 equiv), then 30 min stirring, then third addition of Pd(tBu3P)2 (51 mg, 0.05 equiv) and stirring 30 min. The reaction mixture was quenched with an aqueous saturated solution of NH4Cl (100 mL) and extracted 3 times with ethyl acetate (3×150 mL). The gathered organic phases were filtrated on celite, dried over sodium sulphate. The residue obtained was purified by chromatography on silica gel (Companion system, 40 g Si cartridge) using as eluent a gradient cyclohexane/ethyl acetate 100:0, then 100:0 to 90:10. Evaporation afforded the title compound (336 mg) as a white solid.

Workup

  1. customto reach room temperature
  2. stirringAfter stirring 30 minutes
  3. stirring30 min stirring
  4. stirringstirring 30 min
  5. customThe reaction mixture was quenched with an aqueous saturated solution of NH4Cl (100 mL)
  6. extractionextracted 3 times with ethyl acetate (3×150 mL)
  7. filtrationThe gathered organic phases were filtrated on celite
  8. dry with materialdried over sodium sulphate
  9. customThe residue obtained
  10. customwas purified by chromatography on silica gel (Companion system, 40 g Si cartridge)
  11. customEvaporation

Sources & evidence

ORD record
ord-198f55e376a5449c912793a4ba6231ff
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

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