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

HRID 537484

反応式

HRID 537484 の反応式
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

参加物

7

反応物 3

HCID 142891Ethyl 4-iodobenzoateHCID 205352373,3-Dimethylcyclobutane-1-carbonyl chlorideHCID 178418918HCID 178418918、化合物

生成物 1

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

試薬・触媒・溶媒 3

HCID 83717Copper iodide触媒HCID 313Hydrochloric Acid溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

In a 3-neck flask at −30° C. (monitored with thermalcouple) 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-dimethylcyclobutane carbonyl 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.

後処理

  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)

出典と根拠

ORDレコード
ord-502029a10f554724aa09d2e4b9ca88b3
出典データセット
uspto-grants-2014_10
特許番号
US08859591B2

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