2-Fluorophenol → HCID 28411324, compound

HRID 911255Notes

Reaction equation

HRID 911255 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[OH:17].CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.[Cu]Cl>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[O:17][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 97072-FluorophenolHCID 10796Cesium carbonateHCID 12162Benzonitrile, 4-bromo-HCID 707002,2,6,6-Tetramethyl-3,5-heptanedione

Product 1

HCID 28411324HCID 28411324, compoundYield 66.4%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

Mix under argon atmosphere 4-bromobenzonitrile (2.0 g, 11.3 mmol), 2-fluorophenol (2.5 g, 22.6 mmol), 2,2,6,6-tetramethylheptane-3,5-dione (203 mg, 1.1 mmol), and cesium carbonate (7.4 g, 22.6 mmol) in anhydrous NMP (19 mL). Degas the flask, fill with argon and add copper(I) chloride (554 mg, 5.6 mmol) quickly. Degas the flask then fill with argon and heat at 120° C. for 3 h. Cool to ambient temperature, dilute with EtOAc, filter and wash the filtrate sequentially with 2M aqueous HCl, 0.3M aqueous HCl, 2M aqueous NaOH and brine. Separate the organic layer, dry over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 9:1) to obtain the desired intermediate (1.6 g, 66%). MS (ES+) m/z: 231 (M+NH4)+.

Workup

  1. customDegas the flask
  2. customDegas the flask
  3. temperatureCool to ambient temperature
  4. additiondilute with EtOAc
  5. filtrationfilter
  6. washwash the filtrate sequentially with 2M aqueous HCl, 0.3M aqueous HCl, 2M aqueous NaOH and brine
  7. customSeparate the organic layer
  8. dry with materialdry over Na2SO4
  9. concentrationconcentrate in vacuo
  10. customPurify by chromatography on silica gel eluting with hexane/EtOAc (1:0 and 9:1)

Sources & evidence

ORD record
ord-05eb2bdf9bda4564b279fd29229ba0f4
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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