Ammonia → Tazofelone

温度

0 °C

To 3.22 g (9.2 mmol) of 5-{[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]}-methyl-2-thioxo-4-thiazolidinone, in a 25 mL pressure tube equipped with magnetic stir bar, 13 mL of methanol was added. The resulting reaction mixture was cooled to 0° C. and ammonia gas (1.6 g, 91 mmol) was slowly added. Formalin (0.76 mL, 0.8 g, 10 mmol) was then added. The pressure tube was sealed and heated to 80° C. for approximately 17 hours with stirring. Reaction was deemed complete when the amount of thiolamide was below 4%, as determined by HPLC. Deionized water (12 mL) was then added in a drop-wise manner, followed by acetic acid (6 mL). After 30 min, the reaction mixture was cooled to 0° C. for 1 hour. The reaction mixture was filtered and the resulting crystalline product was dissolved in ethyl acetate (5 vol). Dissolution was facilitated by heating to 66° C. The resulting solution was filtered and seeded with a small amount of 5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl-4-thiazolidinone as the solution was slowly cooled to ambient temperature. Crystallization ensued and the resultant slurry was stirred for approximately 4 hours. The slurry was concentrated under reduced pressure (1 vol ethyl acetate) and stirred for an additional 16 hours. The slurry was filtered and the wet cake was washed with water (2×10 mL) and 1/4 ethyl acetate/hexane (2×10 mL). The product was dried in an oven at 50° C. to obtain 2.07 g (70% yield) of title compound.

1. customThe resulting reaction mixture
2. customThe pressure tube was sealed
3. temperatureheated to 80° C. for approximately 17 hours
4. customReaction
5. temperaturethe reaction mixture was cooled to 0° C. for 1 hour
6. filtrationThe reaction mixture was filtered
7. dissolutionthe resulting crystalline product was dissolved in ethyl acetate (5 vol)
8. dissolutionDissolution
9. temperatureby heating to 66° C
10. filtrationThe resulting solution was filtered
11. temperaturewas slowly cooled to ambient temperature
12. customCrystallization
13. stirringthe resultant slurry was stirred for approximately 4 hours
14. concentrationThe slurry was concentrated under reduced pressure (1 vol ethyl acetate)
15. stirringstirred for an additional 16 hours
16. filtrationThe slurry was filtered
17. washthe wet cake was washed with water (2×10 mL) and 1/4 ethyl acetate/hexane (2×10 mL)
18. customThe product was dried in an oven at 50° C.

ORDレコード

ord-923d112a22f7449c867082b3773ffdc8

出典データセット

uspto-grants-1999_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06005142