Benzene, 1-chloro-4-fluoro- → HCID 18445904, compound

HRID 460325Notes

Reaction equation

HRID 460325 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:9]1(=[O:15])[CH2:13][CH2:12][C:11](=[O:14])[CH2:10]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.Cl[C:38]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=1>CC([O-])=O.CC([O-])=O.[Pd+2].C1COCC1>[F:44][C:41]1[CH:42]=[CH:43][C:38]([CH:10]2[C:11](=[O:14])[CH2:12][CH2:13][C:9]2=[O:15])=[CH:39][CH:40]=1

Participants

7

Reactant 4

HCID 9604Benzene, 1-chloro-4-fluoro-HCID 62657Potassium Phosphate, TribasicHCID 774661,3-CyclopentanedioneHCID 27342152-(Di-tert-butylphosphino)biphenyl

Product 1

HCID 18445904HCID 18445904, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 30.8 mL of THF in a stirred autoclave was added sequentially 17.31 g (81.54 mmol) of K3PO4, 4.0 g (40.8 mmol) of 1,3-cyclopentanedione, 268 mg (0.989 mmol) of 2-(di-t-butylphosphino)biphenyl, 91.5 mg (0.405 mmol) of Pd(OAc)2, and 6.92 g (53.0 mmol) of 1-chloro-4-fluorobenzene. The sides of the reaction vessel were washed with an additional 10 mL of THF and the vessel purged 3 times with vacuum and nitrogen. The heterogeneous reaction mixture was then heated to 100° C., generating 25 psig pressure in the vessel. The reaction was aged at 100° C. for 12 h, cooled to rt and diluted with 150 mL of water. The resulting homogeneous mixture was distilled to remove THF and then heated to 50° C. The aqueous solution was then slowly acidified using conc. HCl until a final pH of 3 was obtained (10.6 mL). The slurry was cooled to rt and filtered. The wet cake was washed with 40 mL of water, 40 mL of toluene, and dried under vacuum at 60° C. for 24 h to give 2-(4-fluorophenyl)-1,3-cyclopentanedione as a light brown solid.

Workup

  1. washThe sides of the reaction vessel were washed with an additional 10 mL of THF
  2. customthe vessel purged 3 times with vacuum and nitrogen
  3. temperaturecooled to rt
  4. additiondiluted with 150 mL of water
  5. distillationThe resulting homogeneous mixture was distilled
  6. customto remove THF
  7. temperatureheated to 50° C
  8. customwas obtained (10.6 mL)
  9. temperatureThe slurry was cooled to rt
  10. filtrationfiltered
  11. washThe wet cake was washed with 40 mL of water, 40 mL of toluene
  12. customdried under vacuum at 60° C. for 24 h

Sources & evidence

ORD record
ord-fde3c7f4e53945fba9beeb1217fc8a6b
Source dataset
uspto-grants-2007_03
Patent number
US07196113B2

Reaction notes

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