Ethyl 4-iodobenzoate → Ethyl 4-(cyclobutyl(hydroxy)methyl)benzoate

HRID 1892693Notes

Reaction equation

HRID 1892693 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.[CH:13]1([CH:17]=[O:18])[CH2:16][CH2:15][CH2:14]1>O1CCCC1>[CH:13]1([CH:17]([OH:18])[C:2]2[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=2)[CH2:16][CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 142891Ethyl 4-iodobenzoateHCID 12431621Cyclobutanecarbaldehyde

Product 1

HCID 68157714Ethyl 4-(cyclobutyl(hydroxy)methyl)benzoateYield 51.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To a solution of ethyl 4-iodobenzoate (1.45 mL, 8.69 mmol) in anhydrous tetrahydrofuran (14.5 mL) at −40° C. was added isopropyl magnesium chloride lithium chloride complex (8.0 mL, 10.4 mmol) dropwise. The resulting brown solution was stirred for 40 min at −40° C. The crude cyclobutanecarbaldehyde (1.8 g, approximately 10.5 mmol pure) was added and the reaction was warmed to room temperature and stirred for 18 h. The reaction is then quenched with 1 N hydrochloric acid and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give 2.0 g of crude material. Purification by silica gel flash chromatography (0-20% ethyl acetate in heptane) afforded ethyl 4-(cyclobutyl(hydroxy)methyl)benzoate (1.05 g) as an oil. 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J=8.4 Hz, 2H), 7.39 (d, J=8.2 Hz, 2H), 4.64 (d, J=7.6 Hz, 1H), 4.47-4.25 (m, 2H), 2.73-2.47 (m, 1H), 2.13-1.94 (m, 2H), 1.95-1.70 (m, 4H), 1.55 (br. s., 1H), 1.38 (t, J=7.0 Hz, 3H).

Workup

  1. temperaturethe reaction was warmed to room temperature
  2. stirringstirred for 18 h
  3. customThe reaction is then quenched with 1 N hydrochloric acid
  4. extractionextracted three times with ethyl acetate
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give 2.0 g of crude material
  9. customPurification by silica gel flash chromatography (0-20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-6ceabafdda914d96a944dd4e2624d75d
Source dataset
uspto-grants-2013_08
Patent number
US08507533B2

Reaction notes

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