Reacción #674306

Ecuación de reacción

Ether

Ethyl chloroformate

4-(benzyloxy)cyclohexanecarbonitrile

LDA

→

ethyl 4-(benzyloxy)-1-cyanocyclohexanecarboxylate

Rendimiento 33.6%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente