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

HRID 2281134Notes

Reaction equation

HRID 2281134 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.[CH3:18][C:19]1([CH3:26])[CH2:22][CH:21]([C:23](Cl)=[O:24])[CH2:20]1>O1CCCC1.Cl.[Cu](I)I>[CH3:18][C:19]1([CH3:26])[CH2:22][CH:21]([C:23]([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:24])[CH2:20]1

Participants

7

Reactant 3

HCID 142891Ethyl 4-iodobenzoateHCID 205352373,3-Dimethylcyclobutane-1-carbonyl chlorideHCID 178418918HCID 178418918, compound

Product 1

HCID 68157422Ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoateYield 74.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In a 3-neck flask at −30° C. (monitored with thermocouple) containing ethyl 4-iodobenzoate (25.0 g, 89.0 mmol) in anhydrous tetrahydrofuran (148 mL) was added isopropylmagnesium chloride (51.0 mL, 20.4 mmol) dropwise over 30 min. and then stirred at the same temperature for another 105 min. Copper iodide (5.07 g, 26.6 mmol) was then added quickly in one portion. The mixture was brought to −20° C. for 25 min. to ensure the solid has dissolved. The reaction is then brought back to −40° C. 3,3-dimethylcyclobutanecarbonyl chloride (15.6 g, 106 mmol) was then added over 5 min. the reaction was then warmed to 0° C. over 4 h. The mixture was then diluted with 1 N HCl and extracted three times with ethyl acetate. The combined organic layers were then washed two times with brine and then dried over sodium sulfate, filtered, and concentrated to provide 26.6 g of crude brown oil. Purification by silica gel flash chromatography twice (0-5% ethyl acetate in heptane) afforded ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoate (17.2 g, 74% yield) as an oil. 1H NMR (400 MHz, CDCl3, δ): 8.11 (d, J=8.2 Hz, 2H), 7.93 (d, J=8.2 Hz, 2H), 4.40 (q, J=7.2 Hz, 2H), 3.89 (quin, J=8.8 Hz, 1H), 2.27-2.14 (m, 2H), 2.12-2.02 (m, 2H), 1.41 (t, J=7.1 Hz, 3H), 1.27 (s, 3H), 1.08 (s, 3H). MS (M+1): 261.2.

Workup

  1. waitThe mixture was brought to −20° C. for 25 min.
  2. dissolutionhas dissolved
  3. customis then brought back to −40° C
  4. extractionextracted three times with ethyl acetate
  5. washThe combined organic layers were then washed two times with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto provide 26.6 g of crude brown oil
  10. customPurification by silica gel flash chromatography twice (0-5% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-c6b553a327a546acae3262a139586bac
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

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