反应详情

Ethyl N-(4-chloro-5-cyclopentyloxy-2-flourophenyl)carbamate (3.01 g, 10 mmol), ethyl 2-hydroxy-3-methyl-3-butenoate (4.32 g, 30 mmol), ferric chloride (162 mg, 1.0 mmol) and tributylamine (92.7 mg, 0.5 mmol) were introduced into a flask (100 cc) equipped with an air condenser tube (20 cm), and the reaction was conducted at 210° C. for 3.5 hours under such a reduced pressure that the ethyl butenoate was refluxed below the middle of the air condenser tube. After the reaction solution was cooled to room temperature, toluene (30 mL) was added, and the reaction solution was washed with 1N sodium hydroxide (20 mL×2) and then 1N hydrochloric acid (20 mL×2). The organic layer was dried over magnesium sulfate. After the drying agent was filtered off, the filtrate was concentrated under reduced pressure. Methanol (3.5 mL) acidified with hydrochloric acid was added to the resulting oily crude product 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, washed with a 4:1 mixed solvent containing of methanol and 6N hydrochloric acid and dried to obtain 3-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)-5-isopropylidene-1,3-oxazolidine-2,4-dione (2.05 g, yield 57.9%).

1. customequipped with an air condenser tube (20 cm)
2. washthe reaction solution was washed with 1N sodium hydroxide (20 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. additionwas added to the resulting oily crude product
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 4:1 mixed solvent
12. additioncontaining of methanol and 6N hydrochloric acid
13. customdried