Reaktion #6631

Reaktionsgleichung

diisopropylamine

diethyl chlorophosphate

lithium diisopropylamide

4,4-dimethyl-6-acetyl-thiochroman

Compound 62

4,4-dimethyl-6-acetyl-thiochroman

n-butyl lithium

diisopropylamine

n-butyllithium

→

title compound

4,4-Dimethyl-6-ethynylthiochroman

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

hexane

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeat -78 degrees C
2. 2
   workup.STIRRINGAfter another hour of stirring at -78 degrees C
3. 3
   Sonstigebrought to room temperature
4. 4
   workup.STIRRINGwhere it was stirred for 3.75 hours
5. 5
   Sonstigeat -78 degrees C
6. 6
   SonstigeThe cooling bath was removed
7. 7
   workup.STIRRINGthe solution stirred at room temperature for 15 hours
8. 8
   Sonstigequenched with water
9. 9
   ExtraktionThe mixture was extracted with 5×50 ml pentane
10. 10
    Waschenthe combined organic fractions washed with 3 N hydrogen chloride, water, saturated NaHCO3 and saturated NaCl
11. 11
    Trocknendried (MgSO4)
12. 12
    SonstigeSolvent was then removed in vacuo
13. 13
    workup.DISTILLATIONthe residue purified by kugelrohr distillation (100 degrees C., 0.7 mm)

Vorschrift

To a solution of 1.441 g (14.2405 mmol) of diisopropylamine in 30 ml dry tetrahydrofuran under argon at -78 degrees C. was added dropwise 9 ml of 1.6 M (14.4 mmol) n-butyl lithium in hexane. After stirring this solution at -78 degrees C. for 1 hour, it was treated dropwise with a solution of 2.95 g (13.389 mmol) of 4,4-dimethyl-6-acetyl-thiochroman (Compound 62) in 5 ml of dry tetrahydrofuran. After another hour of stirring at -78 degrees C., the solution was treated with 2.507 g (14.53 mmol) of diethyl chlorophosphate and brought to room temperature, where it was stirred for 3.75 hours. This solution was then transferred using a double ended needle to a solution of lithium diisopropylamide [prepared using 2.882 g (28.481 mmol) of diisopropylamine and 18 ml of 1.6 M (28.8 mmol) n-butyllithium in hexane] in 60 ml dry tetrahydrofuran at -78 degrees C. The cooling bath was removed and the solution stirred at room temperature for 15 hours, then quenched with water and acidified to pH 1 with 3N hydrogen chloride. The mixture was extracted with 5×50 ml pentane and the combined organic fractions washed with 3 N hydrogen chloride, water, saturated NaHCO3 and saturated NaCl, then dried (MgSO4). Solvent was then removed in vacuo, and the residue purified by kugelrohr distillation (100 degrees C., 0.7 mm) to give the title compound as a pale yellow solid. PMR (CDCl3): & 1.34 (6H, s), 1.94-1.99 (2H, m), 3.04-3.08 (3H, m), 7.06 (1H, d, J~8.4 Hz), 7.17 (1H, dd, J~8.4 Hz, 2.1 Hz), 7.51 (1H, d, J~2.1 Hz).

Quelle