Reaction #674306

Reaction equation

Ether

Ethyl chloroformate

4-(benzyloxy)cyclohexanecarbonitrile

LDA

→

ethyl 4-(benzyloxy)-1-cyanocyclohexanecarboxylate

Yield 33.6%

Solvents

THF

Conditions

Workup

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

Procedure

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.

Source