Reaction #2146738

Reaction equation

diisopropylamine

n-butyl lithium

1-(rel-(1R,2S,6S)-6-ethyl-2-methylcyclohex-3-enyl)ethan-1-one

HCl

acetaldehyde

→

(2E)-1-(rel-(1R,2S,6S)-6-ethyl-2-methylcyclohex-3-enyl)but-2-en-1-one

Yield 56.0%

Solvents

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Temperaturecooled to −78° C.
2. 2
   Temperaturecooled to −78° C.
3. 3
   workup.STIRRINGAfter 1 h stirring
4. 4
   Temperaturethe reaction mixture warmed to 20° C
5. 5
   ExtractionThe aq. phase was extracted with diethyl ether
6. 6
   Dryingphases dried (MgSO4)
7. 7
   Concentrationconcentrated
8. 8
   workup.ADDITIONA solution of the residue (4.9 g) in toluene (4.9 ml) was treated with para-toluene sulfonic acid monohydrate (20 mg)
9. 9
   Temperaturerefluxed overnight
10. 10
    TemperatureThe reaction mixture was cooled
11. 11
    workup.ADDITIONtreated with a saturated aqueous solution of NaHCO3
12. 12
    Extractionthe aqueous phase was extracted with diethyl ether
13. 13
    DryingThe combined organic phases were dried (MgSO4)
14. 14
    Concentrationconcentrated

Procedure

At −78° C., a solution of diisopropylamine (6.6 g, 34 mmol) in tetrahydrofuran (23 ml) was treated with n-butyl lithium (21 ml, 1.6M in hexane, 34 mmol). The resulting solution was warmed to 0° C., cooled to −78° C., and treated with a solution of 1-(rel-(1R,2S,6S)-6-ethyl-2-methylcyclohex-3-enyl)ethan-1-one (4.5 g, 27 mmol) in tetrahydrofuran (23 ml). The resulting solution was stirred 20 min. at −20° C., cooled to −78° C. and treated with a solution of acetaldehyde (1.8 g, 41 mmol) in tetrahydrofuran (23 ml). After 1 h stirring, aqueous 1N HCl (50 ml) was added and the reaction mixture warmed to 20° C. The aq. phase was extracted with diethyl ether and the combined org. phases dried (MgSO4), and concentrated. A solution of the residue (4.9 g) in toluene (4.9 ml) was treated with para-toluene sulfonic acid monohydrate (20 mg) and refluxed overnight. The reaction mixture was cooled, treated with a saturated aqueous solution of NaHCO3 and the aqueous phase was extracted with diethyl ether. The combined organic phases were dried (MgSO4) and concentrated. FC (550 g SiO2, hexane/diethyl ether 9:1) of the crude product gave (2E)-1-(rel-(1R,2S,6S)-6-ethyl-2-methylcyclohex-3-enyl)but-2-en-1-one (2.9 g, 56%).

Source