Toluene → 5-Bromo-3,3-dimethyl-7-isopropyl-2,3-dihydro-benzofuran

Temperature

80 °C

A solution of 5-bromo-3,3,7-trimethyl-2,3-dihydro-benzofuran (Compound 7, 0.6 g, 2.5 mmol), benzophenone imine (0.54 g, 3 mmol), sodium-tert-butoxide (0.34 g, 3.5 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.014 g, 0.01 5 mmol) and (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.029 g, 0.047 mmol) in 10mL of anhydrous toluene was sparged with argon and heated at 80° C. for overnight. The reaction mixture was cooled to ambient temperature, diluted with diethyl ether and filtered. The filtrate was evaporated in vacuo and the residue was dissolved in 7 mL of tetrahydrofiran and treated with 1 mL of 2M hydrochloric acid, and stirred at ambient temperature for 0.5 hour. The volatiles were removed by distillation in vacuo and the residue was dissolved in 0.5M hydrochloric acid and washed with 1:1 hexanes: ethyl acetate. The aqueous phase was neutralized with saturated sodium bicarbonate solution and extracted with dichloromethane. The combined organic extracts were dried over anhydrous sodium sulfate, filtered and evaporated to afford the title compound as a dark brown oil (0.16 g, 36%). 1H-NMR (300 MHz, CDCl3): δ 6.33 (s, 2H), 4.18(s, 2H), 2.16(s, 3H), 1.30(s, 3H).

1. temperatureThe reaction mixture was cooled to ambient temperature
2. filtrationfiltered
3. customThe filtrate was evaporated in vacuo
4. dissolutionthe residue was dissolved in 7 mL of tetrahydrofiran
5. additiontreated with 1 mL of 2M hydrochloric acid
6. customThe volatiles were removed by distillation in vacuo
7. dissolutionthe residue was dissolved in 0.5M hydrochloric acid
8. washwashed with 1:1 hexanes
9. extractionextracted with dichloromethane
10. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
11. filtrationfiltered
12. customevaporated

ORD record

ord-e9cce3c8903748b2854f11cd3ce787d6

Source dataset

uspto-grants-2000_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06093838