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

HRID 2281125Notes

Reaction equation

HRID 2281125 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.[CH3:13][C:14]1([CH3:21])[CH2:17][CH:16]([C:18](Cl)=[O:19])[CH2:15]1>O1CCCC1.Cl.[Cu]I>[CH2:9]([O:8][C:6](=[O:7])[C:5]1[CH:11]=[CH:12][C:2]([C:18]([CH:16]2[CH2:17][C:14]([CH3:21])([CH3:13])[CH2:15]2)=[O:19])=[CH:3][CH:4]=1)[CH3:10]

Participants

6

Reactant 2

HCID 142891Ethyl 4-iodobenzoateHCID 205352373,3-Dimethylcyclobutane-1-carbonyl chloride2×

Product 1

HCID 68157422Ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoateYield 104.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

Ethyl 4-iodobenzoate (600 mg, 2.17 mmol) was dissolved in tetrahydrofuran (6.0 mL) and brought to −40° C. Isopropylmagnesium chloride lithium chloride complex solution (1.0 M in tetrahydrofuran, 0.365 mL, 2.17 mmol) was added dropwise and the yellow-red solution was stirred at −40° C. for 40 min. CuI (124 mg, 0.65 mmol) was added in one portion and the mixture was then stirred at −15° C. for 20 min to dissolve all the solids. The yellow solution was then brought back to −40° C. and 3,3-dimethylcyclobutanecarbonyl chloride (Intermediate 22) (450 mg, 3.07 mmol) was added dropwise. The color changed from slightly green to yellow, then red, then yellow. The mixture was warmed to 0° C. over 2 h in the same bath. The mixture was diluted with 1 N HCl and extracted with ethyl acetate (3 times). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude material was partially purified by silica gel flash chromatography (ethyl acetate/heptane) to give impure 4-(3,3-dimethyl-cyclobutanecarbonyl)-benzoic acid ethyl ester (588 mg). 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J=8.4 Hz, 2 H) 7.94 (d, J=8.4 Hz, 2 H) 4.38-4.48 (m, 2 H) 3.90 (quin, J=8.8 Hz, 1 H) 2.16-2.29 (m, 2 H) 2.04-2.13 (m, 2 H) 1.42 (t, J=7.2 Hz, 3 H) 1.28 (s, 3 H) 1.09 (s, 3 H); MS (M+1): 261.4.

Workup

  1. custombrought to −40° C
  2. stirringthe mixture was then stirred at −15° C. for 20 min
  3. dissolutionto dissolve all the solids
  4. customwas then brought back to −40° C.
  5. temperatureThe mixture was warmed to 0° C. over 2 h in the same bath
  6. extractionextracted with ethyl acetate (3 times)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude material was partially purified by silica gel flash chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-fa4a9c1313dd4fa39712a3a6b4a037b3
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

Loading…