Реакция #674306

Уравнение реакции

Ether

Ethyl chloroformate

4-(benzyloxy)cyclohexanecarbonitrile

LDA

→

ethyl 4-(benzyloxy)-1-cyanocyclohexanecarboxylate

Выход 33.6%

Растворители

THF

Условия реакции

Обработка

1. 1
   workup.STIRRINGThe solution was stirred at −78° C.
2. 2
   Температураto warm to room temperature slowly
3. 3
   workup.STIRRINGstirred overnight
4. 4
   ДругоеThe reaction was quenched by addition of H2O (20 mL), HCl (1.0 N, 20 mL)
5. 5
   ЭкстракцияIt was then extracted with EtOAc (3×40 mL)
6. 6
   ПромывкаThe combined organic solution was washed with brine (50 mL)
7. 7
   Сушкаdried over anhydrous Na2SO4
8. 8
   Концентрированиеconcentrated
9. 9
   Другоеto give pale yellow residue
10. 10
    workup.STIRRINGstirred for 5 min
11. 11
    Фильтрацияfiltered
12. 12
    Другоеto remove the white solid
13. 13
    КонцентрированиеThe ethereal solution was concentrated
14. 14
    Другоеto give the yellow oil which
15. 15
    Другоеwas purified by CombiFlash (25 g silica gel column, EtOAc/Hexane: 0-20%)

Методика

To a solution of 4-(benzyloxy)cyclohexanecarbonitrile (1.26 g, 5.85 mmol, 1.0 equiv) in THF (dry, 30 mL) was added a solution of LDA (3.95 mL, 2.0 M Heptane/THF/toluene, 1.35 equiv) dropwise at −78° C. under N2. The resulting yellow solution was stirred at −78° C. for 2 hrs. Ethyl chloroformate (2.79 mL, 29.26 mmol, 5.0 equiv) was then added by syringe dropwise. The solution was stirred at −78° C. and allowed to warm to room temperature slowly and stirred overnight. The reaction was quenched by addition of H2O (20 mL), HCl (1.0 N, 20 mL). It was then extracted with EtOAc (3×40 mL). The combined organic solution was washed with brine (50 mL), dried over anhydrous Na2SO4 and then concentrated to give pale yellow residue. Ether (40 mL) was added and stirred for 5 min, filtered to remove the white solid. The ethereal solution was concentrated to give the yellow oil which was purified by CombiFlash (25 g silica gel column, EtOAc/Hexane: 0-20%) to afford 565 mg (yield 33%) of ethyl 4-(benzyloxy)-1-cyanocyclohexanecarboxylate as a pale yellow oil.

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