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

HRID 1366765Notes

Reaction equation

HRID 1366765 reaction equation
[C:1](P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)([CH3:4])(C)[CH3:2].[O-:22]P([O-])([O-])=O.[K+].[K+].[K+].Cl[C:31]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=1.[O:38]1[CH2:43][CH2:42]OCC1>CC([O-])=O.CC([O-])=O.[Pd+2]>[F:37][C:34]1[CH:35]=[CH:36][C:31]([CH:42]2[C:43](=[O:38])[CH2:4][CH2:1][C:2]2=[O:22])=[CH:32][CH:33]=1

Participants

6

Reactant 4

HCID 9604Benzene, 1-chloro-4-fluoro-HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 27342152-(Di-tert-butylphosphino)biphenyl

Product 1

HCID 18445904HCID 18445904, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

The title compound was prepared as described in U.S. Pat. No. 5,750,549 or was obtained from its ½ TEA salt as described in U.S. Pat. No. 6,479,518 and J. Org. Chem., 67, 5993-6000 (2002). In the latter case, the ½ TEA salt was suspended in water, the water was acidified with 2N HCl until the pH was less than 2, and the mixture was extracted twice with ethyl acetate. The ethyl acetate layers were each successively washed with brine, combined, and dried over sodium sulfate. Removal of solvent in vacuo afforded the free acid as a thick oil which solidified on standing. Method B: The title compound was also prepared as follows. To a 100 L flask was charged sequentially 113.3 g (0.50 mol) of Pd(OAc)2, 331.4 g (1.11 mol) of 2-(di-t-butylphosphino)biphenyl, 2.476 kg (25.24 mol) of 1, 3-cyclopentanedione, and 10.72 kg (50.5 mol) of powdered K3PO4. The resulting mixture was degassed (3×) by vacuum/N2 back fills. The vessel was then charged with 26 L of 1, 4-dioxane and 4.28 kg (32.78 mol) of 1-chloro-4-fluorbenzene and the vessel degassed (3×) with vacuum/N2 back fills. The resulting slurry was heated to reflux for 12 h, cooled to rt, and water (23 L) was added. The vessel was rinsed with an additional 6 L of water and the reaction mixture further diluted with an additional 46 L of water. To the homogeneous solution was added 9 L of conc. HCl to adjust the pH to 1 and the solution aged for 2.5 h. The slurry was then filtered and the cake washed with 17 L of water and 17 L of toluene. The solid was then dried at 60° C. for 48 h, providing 2-(4-fluoro-phenyl)-1,3-cyclopentanedione as a light tan solid.

Workup

  1. customThe resulting mixture was degassed (3×) by vacuum/N2
  2. customthe vessel degassed (3×) with vacuum/N2
  3. temperatureThe resulting slurry was heated
  4. temperatureto reflux for 12 h
  5. additionwater (23 L) was added
  6. washThe vessel was rinsed with an additional 6 L of water
  7. additionthe reaction mixture further diluted with an additional 46 L of water
  8. additionTo the homogeneous solution was added 9 L of conc. HCl
  9. filtrationThe slurry was then filtered
  10. washthe cake washed with 17 L of water and 17 L of toluene
  11. customThe solid was then dried at 60° C. for 48 h

Sources & evidence

ORD record
ord-ce333c529a784b41a33c95a7042aad01
Source dataset
uspto-grants-2011_02
Patent number
US07893091B2

Reaction notes

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