Dimethylformamide → 3-(6-Bromo-2-fluoro-3-formyl-phenoxy)-5-chloro-benzonitrile

HRID 559055Notes

Reaction equation

HRID 559055 reaction equation
C([Mg]Cl)(C)C.[Cl:6][C:7]1[CH:8]=[C:9]([CH:12]=[C:13]([O:15][C:16]2[C:21]([Br:22])=[CH:20][CH:19]=[C:18](Br)[C:17]=2[F:24])[CH:14]=1)[C:10]#[N:11].CN([CH:28]=[O:29])C>C1COCC1.C1(C)C=CC=CC=1>[Br:22][C:21]1[C:16]([O:15][C:13]2[CH:12]=[C:9]([CH:8]=[C:7]([Cl:6])[CH:14]=2)[C:10]#[N:11])=[C:17]([F:24])[C:18]([CH:28]=[O:29])=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 669995623-Chloro-5-(3,6-dibromo-2-fluoro-phenoxy)-benzonitrileHCID 178418918HCID 178418918, compound

Product 1

HCID 866184923-(6-Bromo-2-fluoro-3-formyl-phenoxy)-5-chloro-benzonitrileYield 98%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of i-PrMgCl (17.3 mL of a 2 M solution in THF, 1.75 equiv) was added slowly to a solution of the 103 (8.0 g, 19.7 mmol) in toluene (160 mL) at −78 C. The solution was aged for 1.5 h then transferred by cannula to a flask containing DMF (2.3 mL, 1.5 equiv) in toluene (30 mL). The solution was quenched with aqueous NH4Cl, and diluted with EtOAc. The organic layer was separated, washed with brine, dried, and evaporated. The crude product was purified by SiO2 by chromatography eluting with 20% EtOAc/hexanes to afford 6.5 g (98%) of 3-(6-bromo-2-fluoro-3-formyl-phenoxy)-5-chloro-benzonitrile (105) as a yellow solid.

Workup

  1. customthen transferred by cannula to a flask
  2. customThe solution was quenched with aqueous NH4Cl
  3. additiondiluted with EtOAc
  4. customThe organic layer was separated
  5. washwashed with brine
  6. customdried
  7. customevaporated
  8. customThe crude product was purified by SiO2 by chromatography
  9. washeluting with 20% EtOAc/hexanes

Sources & evidence

ORD record
ord-1e362430524f4a96932d41df0bfdffc1
Source dataset
uspto-grants-2011_11
Patent number
US08063064B2

Reaction notes

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