Oxalyl chloride → HCID 23113855, compound

HRID 2376377Notes

Reaction equation

HRID 2376377 reaction equation
[CH:1]([C:4]1[CH:25]=[CH:24][C:7]([CH2:8][C:9]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:10]=2[O:11][C:12]([CH3:17])([CH3:16])[C:13](O)=[O:14])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-]>C1COCC1.CN(C=O)C.ClCCl>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][C:9]2[C:10]3[O:11][C:12]([CH3:17])([CH3:16])[C:13](=[O:14])[C:18]=3[C:19]([CH3:23])=[CH:20][C:21]=2[CH3:22])=[CH:24][CH:25]=1)([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 23113961HCID 23113961, compound

Product 1

HCID 23113855HCID 23113855, compoundYield 64%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(2-(4-isopropylbenzyl)-3,5-dimethylphenoxy)-2-methylpropanoic acid obtained in Reference Example 156 (5.55 g, 16.3 mmol) in THF (50 mL) was added dropwise oxalyl chloride (2.13 mL, 24.5 mmol) with ice-cooling. The mixture was stirred for 20 minutes, and DMF (3 drops) was added thereto, and the mixture was stirred with ice-cooling for 30 minutes, and then, was warmed to room temperature. The solvent was removed by concentration under reduced pressure, and to a solution of the residue in dichloromethane (50 mL) was added aluminum chloride (3.26 g, 24.5 mmol) at −78° C., and the mixture was slowly warmed to room temperature. Ice was added to the reaction solution to separate the organic layer, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with a saturated sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4) to obtain 3.35 g (yield 64%) of 7-(4-isopropylbenzyl)-2,2,4,6-tetramethyl-1-benzofuran-3 (2H)-one as crude product. To a solution of this compound (3.35 g, 10.4 mmol) in acetonitrile (40 mL) was added N-bromosuccinimide (1.85 g, 10.4 mmol) with ice-cooling, and the mixture was stirred for 30 minutes. The reaction solution was warmed to room temperature, to which water was added, which was extracted with ethyl acetate. The combined organic layer was washed with a saturated brine, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:19) to obtain 2.76 g (yield 66%) of 5-bromo-7-(4-isopropylbenzyl)-2,2,4,6-tetramethyl-1-benzofuran-3 (2H)-one as crude product.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred with ice-
  3. temperaturecooling for 30 minutes
  4. customThe solvent was removed by concentration under reduced pressure
  5. temperaturethe mixture was slowly warmed to room temperature
  6. additionIce was added to the reaction solution
  7. customto separate the organic layer
  8. extractionthe aqueous layer was extracted with ethyl acetate
  9. washThe combined organic layer was washed with a saturated sodium hydrogen carbonate solution
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4)

Sources & evidence

ORD record
ord-41232351f0a148e29354819c55b321c4
Source dataset
uspto-grants-2008_12
Patent number
US07465815B2

Reaction notes

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