Hydrochloric Acid → 4-Chloro-2-(2-fluoroethyl)-5-methoxyindan-1-one

HRID 859245Notes

Reaction equation

HRID 859245 reaction equation
[Cl:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C:5]([CH2:19][CH2:20][F:21])(C(OCC)=O)[C:6]2=[O:13].[OH-].[Na+].Cl>C1COCC1.CO.O>[Cl:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH2:19][CH2:20][F:21])[C:6]2=[O:13]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 16726731Ethyl 4-chloro-2-(2-fluoroethyl)-5-methoxy-1-oxoindane-2-carboxylate

Product 1

HCID 167267854-Chloro-2-(2-fluoroethyl)-5-methoxyindan-1-one

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent3×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 4-chloro-2-(2-fluoroethyl)-5-methoxy-1-oxoindane-2-carboxylate (56.4 g of crude product from the previous reaction) in THF (330 mL) was added methanol (50 mL) followed by a solution of methanol (116 mL)/water (166 mL). To the resulting clear red-orange solution was added SN aqueous NaOH (55.7 mL, 279 mmol) gradually during 9 minutes giving a black solution. After 3.5 hours, the reaction was quenched by addition of 12N aqueous HCl (30 mL, 360 mmol) and most of the THF and methanol were removed by rotary evaporation at reduced pressure. The residue was partitioned between EtOAc and water and the organic phase was washed with saturated aqueous NaHCO3 and brine and dried over MgSO4. Filtration and removal of the solvent under reduced pressure gave crude product. Purification by flash chromatography on silica gel (elution with CH2Cl2) gave the product. Re-purification of mixed fractions gave additional product. The combined yield esd 4-chloro-2-(2-fluoroethyl)-5-methoxyindan-1-one which by NMR contained approximately 4% of the undesired 6-chloro-2-(2-fluoroethyl)-5-methoxyindan-1-one regioisomer.

Workup

  1. customgiving a black solution
  2. customwere removed by rotary evaporation at reduced pressure
  3. customThe residue was partitioned between EtOAc and water
  4. washthe organic phase was washed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and removal of the solvent under reduced pressure
  7. customgave crude product
  8. customPurification by flash chromatography on silica gel (elution with CH2Cl2)
  9. customgave the product
  10. customRe-purification of mixed fractions gave additional product

Sources & evidence

ORD record
ord-866a487b7d18434a87264037b3bbd8dd
Source dataset
uspto-grants-2006_12
Patent number
US07151196B2

Reaction notes

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