Hydrochloric Acid → Pentoxazone

Ethyl N-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)carbamate (3.01 g, 10 mmol), isobutyl 2-hydroxy-3-methyl-3-butenoate (4.22 g, 24.5 mmol) and tetrabutylammonium chloride (278 mg, 1.0 mmol) were introduced into a flask (25 cc) equipped with a distillation unit, and the reaction was conducted at 200° C. for 9 hours. After the reaction solution was cooled to room temperature, toluene (20 mL) was added, and then the reaction solution was washed with water (20 mL), then 1N sodium hydroxide (20 mL) and 1N hydrochloric acid (20 mL). The organic layer was dried over magnesium sulfate. After the drying agent was filtered off, the filtrate was concentrated under reduced pressure. To the resulting oily crude product, acidic methanol (3.5 mL) was added to form a homogeneous solution. Then, 6N hydrochloric acid (0.4 mL) was further added, and the solution was left to stand at room temperature. The precipitated crystals were collected by filtration, then washed with a mixed solvent consisting of methanol (8 mL) and 6N hydrochloric acid (0.8 mL) and then water (10 mL) and dried to obtain 3-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)-5-isopropylidene-1,3-oxazolidine-2,4-dione (1.34 g, yield 37.8%).

1. customequipped with a distillation unit
2. washthe reaction solution was washed with water (20 mL)
3. dry with materialThe organic layer was dried over magnesium sulfate
4. filtrationAfter the drying agent was filtered off
5. concentrationthe filtrate was concentrated under reduced pressure
6. additionTo the resulting oily crude product, acidic methanol (3.5 mL) was added
7. customto form a homogeneous solution
8. waitthe solution was left
9. customto stand at room temperature
10. filtrationThe precipitated crystals were collected by filtration
11. washwashed with a mixed solvent
12. dry with materialwater (10 mL) and dried

ORD record

ord-17b59d1b31df4eb28abb4e7f3e34e287

Source dataset

uspto-grants-2000_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06090946