Ammonium Chloride → 2-(3-Bromobenzoyl)-6-fluorobenzonitrile

HRID 1662174Notes

Reaction equation

HRID 1662174 reaction equation
[Cu]C#N.[Br-].[Li+].[I-].[C:7]([C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[Zn+])#[N:8].[Br:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21](Cl)=[O:22].[NH4+].[Cl-]>C1COCC1.O>[Br:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=1)[C:21]([C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([F:15])[C:9]=1[C:7]#[N:8])=[O:22]

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 74377Benzoyl chloride, 3-bromo-HCID 82050Lithium BromideHCID 178418546HCID 178418546, compoundHCID 178510276HCID 178510276, compound

Product 1

HCID 585795012-(3-Bromobenzoyl)-6-fluorobenzonitrileYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of copper(I) cyanide (4.70 g, 52.50 mmol) and lithium bromide (2.63 mL, 105.00 mmol) in THF (65 mL) was added to (2-cyano-3-fluorophenyl)zinc(II) iodide (100 mL, 50 mmol) at −78° C. under an argon atmosphere. The mixture was stirred at r.t. for 1 h and then cooled to −78° C. 3-Bromobenzoyl chloride (6.94 mL, 52.50 mmol) was added dropwise and the mixture was stirred at r.t. for 4 h. NH4Cl (50 mL, sat aq) was added followed by water (50 mL). The THF was removed in vacuo and the aqueous residue was diluted with water (100 mL) and DCM (150 mL). A precipitate was filtered off and the filtrate was added to a separation funnel. The organic layer was separated and the water phase extracted with DCM (100 mL). The combined organics were washed with brine (150 mL), dried over MgSO4, concentrated and purified on a silica gel column eluted with DCM to give the title compound (13.37 g, 88% yield): MS (ES+) m/z 304, 306 [M+H]+.

Workup

  1. temperaturecooled to −78° C
  2. stirringthe mixture was stirred at r.t. for 4 h
  3. customThe THF was removed in vacuo
  4. additionthe aqueous residue was diluted with water (100 mL) and DCM (150 mL)
  5. filtrationA precipitate was filtered off
  6. additionthe filtrate was added to a separation funnel
  7. customThe organic layer was separated
  8. extractionthe water phase extracted with DCM (100 mL)
  9. washThe combined organics were washed with brine (150 mL)
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. custompurified on a silica gel column
  13. washeluted with DCM

Sources & evidence

ORD record
ord-3e32c1f2fa294bebb36b3c1d04900f4b
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

Loading…