Acetic Acid → 2,3-dihydrobenzofuran-4-ol

Temperature

-70 °C

The product of Step 2 (39.25 g) was dissolved in THF (0.5 L) and cooled to −78° C. nBuLi (2.5M in hexanes, 300 mL) was then added dropwise over 30 minutes and the reaction stirred at −70° C. for an additional 45 minutes. The solution was then warmed to 0° C. over 10 minutes and stirred at this temperature for 1 hour. Glacial acetic acid (16 mL) was added followed by 1N NaOH (160 mL) and the layers allowed to separate. The organics were extracted with 1N NaOH (2×80 mL) and the combined aqueous fractions were then washed with TBME (160 mL). TBME (240 mL) was then added and the aqueous layer acidified with 6N HCl. The aqueous layer was re-extracted with TBME (240 mL), and the combined organics stirred over activated charcoal (5 g) for 15 minutes, filtered through Celite, and concentrated in vacuo. The crude product was crystallized from toluene and heptane to yield the title compound (16.8 g, 99%).

1. additionwas then added dropwise over 30 minutes
2. temperatureThe solution was then warmed to 0° C. over 10 minutes
3. stirringstirred at this temperature for 1 hour
4. customto separate
5. extractionThe organics were extracted with 1N NaOH (2×80 mL)
6. washthe combined aqueous fractions were then washed with TBME (160 mL)
7. additionTBME (240 mL) was then added
8. extractionThe aqueous layer was re-extracted with TBME (240 mL)
9. stirringthe combined organics stirred over activated charcoal (5 g) for 15 minutes
10. filtrationfiltered through Celite
11. concentrationconcentrated in vacuo
12. customThe crude product was crystallized from toluene and heptane

ORD record

ord-e80964d85c1149d0a6ac975d328966d8

Source dataset

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06214869B1