Hydrochloric Acid → 1H-Indene-2-carboxylic acid, 5-chloro-2,3-dihydro-1-oxo-, methyl ester

HRID 895817Notes

Reaction equation

HRID 895817 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].Cl[C:6]([CH:8]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=1)[C:9]([O:11][CH3:12])=[O:10])=[O:7].Cl>ClCCCl>[Cl:20][C:16]1[CH:15]=[C:14]2[C:19](=[CH:18][CH:17]=1)[C:6](=[O:7])[CH:8]([C:9]([O:11][CH3:12])=[O:10])[CH2:13]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6451240Aluminum(III) ChlorideHCID 11694578HCID 11694578, compound

Product 1

HCID 110423911H-Indene-2-carboxylic acid, 5-chloro-2,3-dihydro-1-oxo-, methyl esterYield 75.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A total of 9.0 g of anhydrous aluminum chloride was suspended in 151.3 g of 1,2-dichloroethane by stirring in an atmosphere of nitrogen gas and was cooled to 0° C. To the cooled suspension was added dropwise a mixture of 7.98 g of methyl 2-chloroformyl-3-(3′-chlorophenyl)-propionate prepared in Example 1 and 151.3 g of 1,2-dichloroethane held at 5° C. or below, followed by stirring under the same conditions for 2 hours. The reaction mixture was added dropwise to 53.6 g of 1.7% by weight hydrochloric acid cooled at 5° C. or below, followed by stirring under the same conditions for 1 hour. The 1,2-dichloroethane layer was separated from the aqueous layer, and the product was further extracted from the aqueous layer with two portions of 15.1 g of 1,2-dichloroethane. The 1,2-dichloroethane layers were collected and were washed with 33.0 g of water, from which 1,2-dichloroethane was removed under reduced pressure. The concentrated residue was purified by silica gel column chromatography [mobile phase: hexane/ethyl acetate=4/1 (by volume)] to yield 5.21 g of methyl 5-chloro-1-oxo-2,3-dihydroindene-2-carboxylate as a beige solid in a yield of 70% on the basis of 3-(3′-chlorophenyl)-2-methoxycarbonylpropionic acid.

Workup

  1. additionTo the cooled suspension was added dropwise
  2. customheld at 5° C. or below
  3. stirringby stirring under the same conditions for 2 hours
  4. temperaturecooled at 5° C. or below
  5. stirringby stirring under the same conditions for 1 hour
  6. customThe 1,2-dichloroethane layer was separated from the aqueous layer
  7. extractionthe product was further extracted from the aqueous layer with two portions of 15.1 g of 1,2-dichloroethane
  8. customThe 1,2-dichloroethane layers were collected
  9. washwere washed with 33.0 g of water, from which 1,2-dichloroethane
  10. customwas removed under reduced pressure
  11. customThe concentrated residue was purified by silica gel column chromatography [mobile phase: hexane/ethyl acetate=4/1 (by volume)]

Sources & evidence

ORD record
ord-2c98feafc7304a96afd1e9d13d761fa4
Source dataset
uspto-grants-2005_07
Patent number
US06916946B2

Reaction notes

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