2(3H)-Benzofuranone → HCID 14143242, compound

Temperature

-65 °C

A 2000-mL 3-neck flask fitted with nitrogen inlet, low temperature thermometer, and 500-mL pressure equilibrated dropping funnel is flame dried and charged with dry hexane (freshly distilled from calcium hydride, 200 mL). The flask is cooled with an external dry ice/acetone bath then tert-butyl-lithium (1.7 M in pentane, 200 mL, 340 mmol) is added via double ended needle transfer. The resulting solution is cooled to -65° C. internal temperature then a solution of 43 (40.00 g, 294 mmol) in a mixture of ether (100 mL) and hexane (300 mL) is added dropwise over 1 hour at a rate such that the reaction temperature does not exceed -55° C. Upon completion of the addition the reaction mixture is stirred with dry ice/acetone cooling for 10 minutes, the cooling bath is removed and the reaction allowed to gradually warm. After 1 hour the temperature reaches about 5° C. The reaction is quenched by dropwise addition of water (40 mL), followed immediately by 2N HCl (200 mL) and tetrahydrofuran (200 mL). The reaction mixture is then poured into a 4000-mL Erlenmeyer flask containing 2N HCl (200 mL) and the resulting mixture diluted to a total volume of 2800 mL with tetrahydrofuran. The elimination is allowed to proceed for 2.5 hours then 20% NaCl (500 mL) was added and the layers separated. The aqueous layer was reextracted with ether (500 mL) and the combined organic layers washed with 20% NaCl (500 mL), dried (Na2SO4) and concentrated to a reddish oil (48.7 g) which is distilled. The total distillate is chromatographed (Water Prep 500A) using hexane as eluant to afford 4-tert-butyl-6,7-dihydrobenzofuran as a colorless liquid.

1. customA 2000-mL 3-neck flask fitted with nitrogen inlet
2. temperatureis flame
3. customdried
4. additioncharged with dry hexane (
5. distillationfreshly distilled from calcium hydride, 200 mL)
6. temperatureThe flask is cooled with an external dry ice/acetone bath
7. additionis added dropwise over 1 hour at a rate such that the reaction temperature
8. customdoes not exceed -55° C
9. additionUpon completion of the addition the reaction mixture
10. customthe cooling bath is removed
11. temperatureto gradually warm
12. customThe reaction is quenched by dropwise addition of water (40 mL)
13. additionThe reaction mixture is then poured into a 4000-mL Erlenmeyer flask
14. additioncontaining 2N HCl (200 mL)
15. additionthe resulting mixture diluted to a total volume of 2800 mL with tetrahydrofuran
16. waitto proceed for 2.5 hours
17. addition20% NaCl (500 mL) was added
18. customthe layers separated
19. washthe combined organic layers washed with 20% NaCl (500 mL)
20. dry with materialdried (Na2SO4)
21. concentrationconcentrated to a reddish oil (48.7 g) which
22. distillationis distilled
23. distillationThe total distillate is chromatographed (Water Prep 500A)

ORD record

ord-214612e82e2946f388a8a5c1dddbdd6e

Source dataset

uspto-grants-1990_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04966907