Cyclopentanecarbonyl chloride → Ethyl 4-(cyclopentanecarbonyl)benzoate

HRID 537438Notes

Reaction equation

HRID 537438 reaction equation
[Cl-].[Li+].C([Mg]Cl)(C)C.I[C:9]1[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=1.[CH:20]1([C:25](Cl)=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21]1>O1CCCC1.[Cu]I>[CH:20]1([C:25]([C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 78284Cyclopentanecarbonyl chlorideHCID 142891Ethyl 4-iodobenzoateHCID 178461733HCID 178461733, compound

Product 1

HCID 24724161Ethyl 4-(cyclopentanecarbonyl)benzoate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

At −40° C., isopropylmagnesium chloride lithium chloride (13.9 mL, 1.3 M in THF) was added dropwise to a solution of ethyl 4-iodobenzoate (4971 mg, 18.01 mmol) in tetrahydrofuran (30 mL). The solution was stirred at −40° C. for 50 minutes. Copper(I) iodide (1.03 g, 5.4 mmol) was added. The mixture was allowed to warm to −15° C. and stir for 8 minutes. The solution was cooled back to −40° C. and cyclopentanecarbonyl chloride (3580 mg, 27.0 mmol) was added dropwise. The mixture was allowed to gradually warm to 0° C. over 3 hours. The mixture was quenched with 1 N HCl (20 mL) and diluted with ethyl acetate. The mixture was stirred at room temperature for 5 min. A white precipitate formed. The mixture was filtered through celite and the filtrate transferred to a separatory funnel. The layers were separated. The aqueous was extracted twice with ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (0-20% ethyl acetate in heptane) gave ethyl 4-(cyclopentanecarbonyl)benzoate as an oil. 1H NMR (400 MHz, CDCl3, δ): 8.13-8.08 (m, 2H), 8.02-7.97 (m, 2H), 4.39 (q, J=7.22 Hz, 2H), 3.77-3.65 (m, 1H), 1.99-1.79 (m, 4H), 1.77-1.60 (m, 4H), 1.40 (t, J=7.22 Hz, 3H).

Workup

  1. temperatureto warm to −15° C.
  2. stirringstir for 8 minutes
  3. temperatureThe solution was cooled back to −40° C.
  4. temperatureto gradually warm to 0° C. over 3 hours
  5. customThe mixture was quenched with 1 N HCl (20 mL)
  6. additiondiluted with ethyl acetate
  7. stirringThe mixture was stirred at room temperature for 5 min
  8. customA white precipitate formed
  9. filtrationThe mixture was filtered through celite
  10. customthe filtrate transferred to a separatory funnel
  11. customThe layers were separated
  12. extractionThe aqueous was extracted twice with ethyl acetate
  13. washThe combined organics were washed with brine
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customPurification by column chromatography (0-20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-ca1bb9da7b394bb5a0530fddfe05a04b
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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