Diisopropylamine → 1,1,4,4-Tetramethyl-6-ethynyl-1,2,3,4-tetrahydronaphthalene

Temperatur

-78 °C

To a stirred solution of 1.1572 g (11.4359 mmol) of diisopropylamine in 20 ml of dry tetrahydrofuran under argon at -78° C. was added dropwise via syringe, 7.2 ml of 1.6M (11.52 mmol) n-butyllithium in hexane. This mixture was stirred at -78° C. for 1 hour and then treated dropwise with a solution of 2.635 g (11.4391 mmol) of 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-6-acetylnaphthalene in 6 ml of dry tetrahydrofuran. After stirring at -78° C. for 1 hour, the mixture was treated with 1.97 g (11.4175 mmol) of diethyl chlorophosphate. The cooling bath was then removed and the mixture stirred at room temperature for 3.5 hours. This mixture was then transferred using a double ended needle to a solution of lithium diisopropylamide [prepared using 2.31 g (22.83 22 mmol) of diisopropylamine and 14.5 ml of 1.6M (23.2 mmol) n-butyllithium in hexane] in 60 ml of dry tetrahydrofuran at -78° C. Stirring was commenced at room temperature and continued for 20 hours. The reaction was then quenched with 50 ml water and acidified with 25 ml of 3N hydrogen chloride. Reaction product was recovered by extracting with 5×50 ml pentane. Organic extracts were combined and washed with 3N hydrogen chloride, water, saturated NaHCO3 and saturated NaCl solutions and then dried (MgSO4). Solvent was then removed and residue purified by flash chromatography (silica, 5% ethylacetate in hexane) followed by kugelrohr distillation (60° C., 0.2 mm) to give the title compound as a colorless oil. PMR (CDCl3): δ1.25 (6H, s), 1.27(6H, S), 1.66 (4H, s), 2.98 (1H, S, 7.24 (2H, s), 7.46 (1H, s).

1. stirringAfter stirring at -78° C. for 1 hour
2. customThe cooling bath was then removed
3. stirringthe mixture stirred at room temperature for 3.5 hours
4. customat -78° C
5. stirringStirring
6. customwas commenced at room temperature
7. waitcontinued for 20 hours
8. customThe reaction was then quenched with 50 ml water
9. customReaction product
10. customwas recovered
11. extractionby extracting with 5×50 ml pentane
12. washwashed with 3N hydrogen chloride, water, saturated NaHCO3 and saturated NaCl solutions
13. dry with materialdried (MgSO4)
14. customSolvent was then removed
15. customresidue purified by flash chromatography (silica, 5% ethylacetate in hexane)
16. distillationfollowed by kugelrohr distillation (60° C., 0.2 mm)

ORD-Eintrag

ord-4a3046a3faff4e1180cfa37b5a1573a3

Quelldatensatz

uspto-grants-1995_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05466690