Réaction #6641

Équation de réaction

diethyl chlorophosphate

lithium diisopropyl amide

n-butyllithium

diisopropylamine

n-butyl lithium

4,4-dimethyl-6-acetylchroman

Compound 77

4,4-dimethyl-6-acetylchroman

→

title compound

4,4-Dimethyl-6-ethynylchroman

Solvants

tetrahydrofuran

tetrahydrofuran

hexane

Conditions de réaction

Traitement

1. 1
   Séchagedry of tetrahydrofuran
2. 2
   workup.STIRRINGAfter stirring at 31 78 degrees C
3. 3
   workup.WAITfor 1 hour
4. 4
   AutreThe cooling bath was then removed
5. 5
   workup.STIRRINGthe reaction mixture stirred at room temperature for 2.75 hours
6. 6
   Autreat 31 78 degrees C
7. 7
   AutreThe cooling bath was removed
8. 8
   workup.STIRRINGmixture stirred at room temperature for 18 hours
9. 9
   Autrequenched with 50 ml water and 25 ml of 3N hydrogen chloride The mixture
10. 10
    Extractionwas extracted with 2×100 ml and 3×50 ml of pentane
11. 11
    Lavagethe combined organic fractions washed with 3N hydrogen chloride, water, saturated NaHCO3 and saturated NaCl solutions
12. 12
    Séchagedried (MgSO4)
13. 13
    AutreSolvent was then removed in vacuo
14. 14
    Autrethe residue purified by flash chromatography (silica; 10% ethyl acetate in hexane)
15. 15
    workup.DISTILLATIONfollowed by kugelrohr distillation (70 degrees C.; 0.35mm)

Mode opératoire

To a solution of 2.47 g (24.41 mmol) of diisopropylamine in 40 ml dry tetrahydrofuran under argon at 31 78 degrees C was added dropwise 15.2 ml of 1.6M (24.32 mmol) n-butyl lithium in hexane. This mixture was stirred at 31 78 degrees C. for 1 hour and then treated dropwise with a solution of 4.98 g (24.38 mmol) of 4,4-dimethyl-6-acetylchroman (Compound 77) in 1 ml dry of tetrahydrofuran. After stirring at 31 78 degrees C. for 1 hour, the solution was treated with 4.2 g (24.36 mmol) of diethyl chlorophosphate. The cooling bath was then removed and the reaction mixture stirred at room temperature for 2.75 hours. This solution was then transferred using a double ended needle to a solution of lithium diisopropyl amide [prepared using 4.95 g (48.92 mmol) or diisopropylamine and 30.5 ml of 1.6M (48.8 mmol) n-butyllithium in hexane] in 80 ml dry tetrahydrofuran at 31 78 degrees C. The cooling bath was removed and mixture stirred at room temperature for 18 hours and then quenched with 50 ml water and 25 ml of 3N hydrogen chloride The mixture was extracted with 2×100 ml and 3×50 ml of pentane and the combined organic fractions washed with 3N hydrogen chloride, water, saturated NaHCO3 and saturated NaCl solutions and then dried (MgSO4). Solvent was then removed in vacuo and the residue purified by flash chromatography (silica; 10% ethyl acetate in hexane) followed by kugelrohr distillation (70 degrees C.; 0.35mm) to give the title compound as a colorless crystalline solid. PMR (CDCl3): δ 1.33 (6H), 1.81-1.86 (2H, m), 3.00 (1H, s), 4.19-4.24 (2H, m), 6.75 (1H, d, J~8.5 Hz}, 7.22 (1H, dd, J~8.5 Hz, 2.3 Hz), 7.44 (1H, d, J~2 3 Hz).

Source