反应详情

Ethyl N-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)carbamate (19.6 g, 65 mmol), ethyl 2-hydroxy-3-methyl-3-butenoate (15.1 g, 105 mmol), ferric chloride (105 mg, 0.65 mmol) and tributylamine (611 mg, 3.3 mmol) were introduced into a flask (200 cc) equipped with a distillation unit, and the reaction was conducted at 200° C. for 5 hours. After the reaction solution was cooled to room temperature, toluene (100 mL) was added, and then the reaction solution was washed with 1N sodium hydroxide (100 mL×2) and 1N hydrochloric acid (100 mL×2). 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 (15 mL) was added to form a homogeneous solution. Then, 6N hydrochloric acid (2 mL) was further added, and the solution was left to stand at room temperature. The precipitated crystals were collected by filtration, washed with a mixed solvent consisting of methanol (20 mL) and 6N hydrochloric acid (5 mL) and dried to obtain 3-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)-5-isopropylidene-1,3-oxazolidine-2,4-dione (16.7 g, yield 72.5%).

1. customequipped with a distillation unit
2. washthe reaction solution was washed with 1N sodium hydroxide (100 mL×2) and 1N hydrochloric acid (100 mL×2)
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 (15 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. customdried