Acetic Acid → 2-(2-Fluoro-4-methoxyphenyl)-2-propanol

Temperature

30 °C

A solution of 2-fluoro-4-methoxyacetophenone (78.1 g, 460 mmol) in tetrahydrofuran (58.6 ml) was added to 3M methylmagnesium chloride solution in THF (199 ml, 598 mmol) at 20 to 35° C. under a nitrogen atmosphere over 30 min without cooling. Additional THF (19.53 ml) was used to rinse all starting material into the vessel. After complete addition, the mixture was stirred at 30° C. for 10 min., then was quenched into acetic acid (52.6 ml, 920 mmol) and water (273 ml) at 5-25° C. THF (20 ml) was used to rinse the vessel. Heptane (156 ml) was then added. The biphasic mixture was stirred at 20-25° C. for 30 min, and then the organic layer was separated. The organic layer was assayed and was found to contain 83.0 g of the desired product, which corresponds to 98% yield. The organic layer was concentrated under vacuum to remove THF, then was flushed with IPAC (200 ml), and the volume was increased to 500 ml by addition of more IPAC. This was used directly in the next step.

1. temperaturewithout cooling
2. washto rinse all starting material into the vessel
3. additionAfter complete addition
4. washto rinse the vessel
5. additionHeptane (156 ml) was then added
6. stirringThe biphasic mixture was stirred at 20-25° C. for 30 min
7. customthe organic layer was separated
8. concentrationThe organic layer was concentrated under vacuum
9. customto remove THF
10. customwas flushed with IPAC (200 ml)
11. temperaturethe volume was increased to 500 ml by addition of more IPAC

ORD record

ord-8be700fa6cb54655acc79d02c0cc0bb2

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145348B2