1-Bromo-4-tert-butylbenzene → 2-(4-t-butylphenyl)-2-methyl-5-(N-methyl-anilinomethylene)-cyclopentanone

An oven dried Schlenk tube equipped with a rubber septum was cooled under an argon purge. The septum was removed and the tube was charged with palladium acetate (5.6 mg, 0.025 mmol, 5 mol % Pd), (−)-2-(dicyclohexylphosphino)-2′-(dimethylamino)-1,1′-binaphthyl (18.5 mg, 0.038 mmol, 7.5 mol %) and 2-methyl-5-(N-methyl-anilinomethylene) cyclopentanone (108 mg, 0.5 mmol). Toluene (2 mL) was added and the mixture was stirred for 1 min at room temperature. 4-t-Butylbromobenzene (0.17 mL, 1.0 mmol) and sodium t-butoxide (96 mg, 1.0 mmol) were added to the tube, the tube was capped with the septum, purged with argon, and additional toluene (4 mL) was added through the septum. The mixture was heated to 100° C. with stirring until the starting ketone had been completely consumed as judged by GC analysis. The mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride (10 mL) and diluted with ether (20 mL). The mixture was poured into a separatory funnel and the layers were separated. The aqueous layer was extracted with ether (20 mL), and the combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel to afford 173 mg (99%) of the title compound. The ee was determined to be 67% by chiral HPLC analysis.

1. customAn oven dried Schlenk tube
2. customequipped with a rubber septum
3. temperaturewas cooled under an argon
4. custompurge
5. customThe septum was removed
6. customthe tube was capped with the septum
7. custompurged with argon, and additional toluene (4 mL)
8. additionwas added through the septum
9. temperatureThe mixture was heated to 100° C.
10. stirringwith stirring until the starting ketone
11. customhad been completely consumed
12. temperatureThe mixture was cooled to room temperature
13. customquenched with saturated aqueous ammonium chloride (10 mL)
14. additiondiluted with ether (20 mL)
15. additionThe mixture was poured into a separatory funnel
16. customthe layers were separated
17. extractionThe aqueous layer was extracted with ether (20 mL)
18. washthe combined organic layers were washed with brine (20 mL)
19. dry with materialdried over anhydrous magnesium sulfate
20. filtrationfiltered
21. concentrationconcentrated in vacuo
22. customThe crude material was purified by flash chromatography on silica gel

ORD-Eintrag

ord-ef86e0d25b5c42f395bd06ab9a9b0340

Quelldatensatz

uspto-grants-2005_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06867310B1