Ethyl 4-iodobenzoate → Ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoate

HRID 537461

Reaction equation

HRID 537461 reaction equation
I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[Cl-].[Li+].[CH3:20][C:21]1([CH3:28])[CH2:24][CH:23]([C:25](Cl)=[O:26])[CH2:22]1>O1CCCC1.[Cu]I>[CH3:20][C:21]1([CH3:28])[CH2:24][CH:23]([C:25]([C:2]2[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=2)=[O:26])[CH2:22]1

Participants

6

Reactant 3

HCID 142891Ethyl 4-iodobenzoateHCID 205352373,3-Dimethylcyclobutane-1-carbonyl chlorideHCID 178461733HCID 178461733, compound

Product 1

HCID 68157422Ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoateYield 83.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a −40° C. solution of ethyl 4-iodobenzoate (2.30 g, 8.30 mmol) in tetrahydrofuran (20 mL) was added isopropylmagnesium chloride-lithium chloride (7.1 mL, 1.3 M in THF, 9.2 mmol) dropwise. The mixture was stirred for 1 hour at −40° C. Copper(I) iodide (476 mg, 2.50 mmol) was then added and the reaction was allowed to warm to −10° C. and stir for 20 minutes. The solution was cooled again to −40° C. and a solution of the previously prepared 3,3-dimethylcyclobutanecarbonylchloride (1.54 g, 10.5 mmol) in tetrahydrofuran (10 mL) was added dropwise. The reaction was allowed to warm to 0° C. and stir for 2 hours. The reaction was quenched with 1 N aqueous hydrochloric acid and extracted with ethyl acetate (3×15 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography gave ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoate (1.80 g, 83%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3, δ): 8.15 (d, J=8.4 Hz, 2H), 7.98 (d, J=8.4 Hz, 2H), 4.20-4.47 (m, 2H), 3.89-3.98 (m, 1H), 2.22-2.27 (m, 2H), 2.09-2.15 (m, 2H), 1.45 (t, J=7.2 Hz, 3H), 1.32 (s, 3H), 1.13 (s, 3H).

Workup

  1. temperatureto warm to −10° C.
  2. stirringstir for 20 minutes
  3. temperatureThe solution was cooled again to −40° C.
  4. temperatureto warm to 0° C.
  5. stirringstir for 2 hours
  6. customThe reaction was quenched with 1 N aqueous hydrochloric acid
  7. extractionextracted with ethyl acetate (3×15 mL)
  8. dry with materialThe combined organics were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-3ab9950b59ba4af6803cc808d9540fb0
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Linked notes

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