Diisopropylamine → 1,1,4,4,7-Pentamethyl-6-ethynyl-1,2,3,4-tetrahydronaphthalene

Temperature

-78 °C

To a stirred solution of 794.2 mg (7.8486 mmol) diisopropylamine in 7 ml dry tetrahydrofuran under argon at -78° C. was added dropwise 4.9 ml of 1.6M (7.84 mmol) n-butyllithium in hexane. This solution was stirred at -78° C. for 1.25 hours and then treated via a double ended needle with a solution of 1.9 g (7.7749 mmol) of 1,1,4,4,7-pentamethyl-6-acetyl-1,2,3,4-tetrahydronapthalene in 4 ml dry tetrahydrofuran. After stirring at -78° C. for 1 hour, the mixture was treated with 1.3134 g (7.6117 mmol) of diethyl chlorophosphate. The cooling bath was removed and mixture stirred at room temperature for 3 hours. This material was then transferred using a double ended needle into a solution of lithium diisopropylamide [prepared as above using 1.5884 g (15.6972 mmol) of diisopropylamine and 10 ml of 1.6M (16 mmol) n-butyllithium in hexane]in 15 ml dry tetrahydrofuran at -78° C. The cooling bath was removed and mixture stirred at room temperature for 15 hours, then quenched with 50 ml water, and acidified to pH 1 with 3N hydrogen chloride. The mixture was extracted with 3×75 ml petroleum ether and the organic extracts were combined, washed with saturated NaHCO3 and saturated NaCl solutions and dried (MgSO4). Solvent was then removed in vacuo and the residue purified by flash chromatography (silica; 3% ethyl acetate in hexane) followed by kugelrohr distillation (50° C., 0.05 mm) to give the title compound as a colorless oil. PMR (CDCl3): δ1.28 (12 H, s), 1.67 (4 H, s), 1.42 (3 H, s), 3.20 (1 H, s), 7.15 (1 H, s), 7.44 (1 H, s).

1. additiontreated via
2. stirringAfter stirring at -78° C. for 1 hour
3. customThe cooling bath was removed
4. stirringmixture stirred at room temperature for 3 hours
5. customat -78° C
6. customThe cooling bath was removed
7. stirringmixture stirred at room temperature for 15 hours
8. customquenched with 50 ml water
9. extractionThe mixture was extracted with 3×75 ml petroleum ether
10. washwashed with saturated NaHCO3 and saturated NaCl solutions
11. dry with materialdried (MgSO4)
12. customSolvent was then removed in vacuo
13. customthe residue purified by flash chromatography (silica; 3% ethyl acetate in hexane)
14. distillationfollowed by kugelrohr distillation (50° C., 0.05 mm)

ORD record

ord-f6572f03311442eaabd3eed776db3701

Source dataset

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05246962