乙醚 → (1-HYDROXYMETHYL-CYCLOPROPYL)-ACETIC ACID METHYL ESTER

HRID 22427

反应方程式

HRID 22427 反应方程式
C([O:9][CH2:10][C:11]1([CH2:14][C:15]#N)[CH2:13][CH2:12]1)(=O)C1C=CC=CC=1.[OH-:17].[K+].[N+](=C)=[N-].CC[O:24][CH2:25]C>C(O)C.CCCCCC>[OH:9][CH2:10][C:11]1([CH2:14][C:15]([O:24][CH3:25])=[O:17])[CH2:12][CH2:13]1

参与物

7

反应物 4

HCID 3283乙醚HCID 9550重氮甲烷HCID 14797氢氧化钾HCID 29941744[1-(Cyanomethyl)cyclopropyl]methyl benzoate

产物 1

HCID 29941748(1-HYDROXYMETHYL-CYCLOPROPYL)-ACETIC ACID METHYL ESTER收率 50%

试剂、催化剂与溶剂 2

HCID 702乙醇溶剂HCID 8058正己烷溶剂

反应条件

温度
10 °C

实验过程

The nitrile of Step 3 (0.388 mol) was dissolved in ethanol (400 mL), 8N KOH (800 mL) was added and the reaction mixture was heated to reflux overnight. Most of the ethanol was evaporated and ice was added to the mixture. Concentrated HCl was added (600 mL) dropwise at 0° C. (without warming over 10° C. inside the solution) until obtention of pH approx. 1. The acid was then extracted with EtOAc two times and the organic phases were washed 2 times with brine and dried over Na2SO4. The solvent was evaporated and the solid was dissolved in THF (500 mL). A solution of diazomethane in Et2O (about 1.7 L, 0.85 mol) was added at 0° C. until the yellow color remained and no more acid could be seen by TLC. The solvent was evaporated and the residual oil was purified by flash chromatography using 1:1 to 2:1 EtOAc:hexane to yield 28.2 g, (50% yield) of the title compound. 1H NMR (CDCl3) δ0.55 (4H, m), 2.45 (2H, s), 2.55 (1H, t), 3.5 (2H, d), 3.70 (3H, s).

后处理

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux overnight
  3. customMost of the ethanol was evaporated
  4. additionice was added to the mixture
  5. additionConcentrated HCl was added (600 mL) dropwise at 0° C. (
  6. extractionThe acid was then extracted with EtOAc two times
  7. washthe organic phases were washed 2 times with brine
  8. dry with materialdried over Na2SO4
  9. customThe solvent was evaporated
  10. dissolutionthe solid was dissolved in THF (500 mL)
  11. customThe solvent was evaporated
  12. customthe residual oil was purified by flash chromatography

来源与证据

ORD记录
ord-6580c9e7e82d451093839be42a1b70af
来源数据集
uspto-grants-1995_06
专利号
US05428033

关联笔记

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