Reaction #1605783

Reaction equation

NH4Cl

THF

lithium diisopropylamide

THF

hexane

Cyclohexanone

→

solid

Yield 80.7%

1-[cyano-(4-methoxyphenyl)methyl]cyclohexanol

Yield 80.7%

Conditions

Workup

1. 1
   Temperaturemaintaining the reaction temperature below −65° C
2. 2
   Otherdid not rise above −65° C
3. 3
   workup.ADDITIONAfter the addition reaction
4. 4
   workup.STIRRINGwas stirred at −78° C. for 2 hours
5. 5
   workup.ADDITIONcontaining ice
6. 6
   workup.STIRRINGThe mixture was stirred for 15 minutes
7. 7
   Extractionwas extracted with ethyl acetate (4×200 mL)
8. 8
   WashCombined ethyl acetate layer was washed with water (3×100 mL), brine (1×10 mL)
9. 9
   Dryingdried (Na2SO4)
10. 10
    OtherEthyl acetate was evaporated in vacuo
11. 11
    Otherto give colorless solid
12. 12
    FiltrationThe precipitate was filtered
13. 13
    Washwashed with hexane
14. 14
    Otherdried in vacuo

Procedure

A solution of 4-methoxybenzylnitrile (53.5 g, 0.36 mol) in 400 mL THF was cooled to −78° C. followed by slow addition of a 2.0 M THF solution of lithium diisopropylamide (200 nm, 0.40 mol) maintaining the reaction temperature below −65° C. The reaction was stirred at −78° C. for 30 minutes. Cyclohexanone (39.5 g, 0.40 mol) was added at a rate such that the reaction temperature did not rise above −65° C. After the addition reaction was stirred at −78° C. for 2 hours, then was poured into 1 L saturated aqueous NH4Cl containing ice. The mixture was stirred for 15 minutes and was extracted with ethyl acetate (4×200 mL). Combined ethyl acetate layer was washed with water (3×100 mL), brine (1×10 mL) and dried (Na2SO4). Ethyl acetate was evaporated in vacuo to give colorless solid that was trichurated with hexane. The precipitate was filtered, washed with hexane, dried in vacuo to give colorless solid (72.0 g, 80.7% yield). 1H (CDCl3): 7.30 and 6.90 (q, 4H), 3.80 (s, 3H), 3.75 (s, 1H), 1.55 (m, 10H); 13C (CDCl3): 159.8, 130.8, 123.8, 120.0, 114.1, 72.9, 55.5, 49.5, 34.9, 25.3, 21.6.

Source