(4-Chlorophenyl)acetic acid → 2-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)ethan-1-one

HRID 2101737Notes

Reaction equation

HRID 2101737 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]([OH:21])=O)=[CH:14][CH:13]=1.[Cl:22][C:23]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:24]=1C(OC)=O>C1COCC1>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][C:19]([C:30]2[CH:29]=[CH:24][C:23]([Cl:22])=[CH:32][C:31]=2[Cl:33])=[O:21])=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 15880(4-Chlorophenyl)acetic acidHCID 37055Methyl 2,4-dichlorobenzoateHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 219848672-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)ethan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

A 5 L round bottom flask equipped with an addition funnel, N2 inlet, thermometer and a mechanical stirrer was charged with 387 mL of 1M sodium bis-trimethylsilylamide in TBF and cooled to −60° C. A solution of 230 g (1.35 mol) of 4-chlorophenylacetic acid in 300 mL of THF was added keeping the temperature below −40° C. After stirring the mixture for 90 min at −70° C., 264 g (1.29 mol) of methyl 2,4-dichlorobenzoate was added over 20 min. The solution was stirred for 40 min at −70° C., the cooling bath was removed and the mixture was allowed to warm to 0° C. Reaction was quenched by pouring into 4 L of 2N HCl and ice and extracted with ether. Each ether layer was washed with saturated NaHCO3, brine, dried with MgSO4 and filtered through a 2″ plug of silica gel. The filtrate was concentrated to ca. 1 lit of a slushy liquid which was diluted with 1 L of hexane and cooled in a refrigerator. The solid formed was filtered, washed with hexane and dried. A second crop was isolated by concentrating the mother liquors. The two crops of crystals were combined.

Workup

  1. customA 5 L round bottom flask equipped with an addition funnel, N2 inlet
  2. customthe temperature below −40° C
  3. stirringThe solution was stirred for 40 min at −70° C.
  4. customthe cooling bath was removed
  5. temperatureto warm to 0° C
  6. customReaction
  7. customwas quenched
  8. additionby pouring into 4 L of 2N HCl and ice
  9. extractionextracted with ether
  10. washEach ether layer was washed with saturated NaHCO3, brine
  11. dry with materialdried with MgSO4
  12. filtrationfiltered through a 2″ plug of silica gel
  13. concentrationThe filtrate was concentrated to ca. 1 lit of a slushy liquid which
  14. additionwas diluted with 1 L of hexane
  15. temperaturecooled in a refrigerator
  16. customThe solid formed
  17. filtrationwas filtered
  18. washwashed with hexane
  19. customdried
  20. customA second crop was isolated
  21. concentrationby concentrating the mother liquors

Sources & evidence

ORD record
ord-9f500a7df6d14639bb1084316481e387
Source dataset
uspto-grants-2009_08
Patent number
US07572785B2

Reaction notes

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