反应详情

To a stirred solution of 100 mg of 3-{4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-phenyl}-4H-[1,2,4]oxadiazol-5-one in 3 mL of dichloromethane at −70° C. was added 0.34 mL of a 1M solution of boron tribromide in dichloromethane. After 1 h at −60° C., TLC monitoring (dichloromethane/acetone 8/2) showed remaining starting material so 1 mL of a 1M solution of boron tribromide in dichloromethane was added. After 10 min, the reaction mixture was poured into 30 mL of methanol and was neutralised with 5 mL of a saturated aqueous solution of NaHCO3. The suspension was filtered and the filtrate was concentrated under reduced pressure. The residue was taken up into dichloromethane then water added. The aqueous layer was separated and extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 60 mg of crude product. Purification by column chromatography on silica gel (dichloromethane 1/acetone 1) gave 13 mg of a first batch of the title compound (purity >95%) and 50 mg of a second batch of the title compound (purity >90%). The second batch was repurified by column chromatography on silica gel (dichloromethane 90/methanol 10). A total of 48 mg of 3-{2-fluoro-4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one was obtained.

1. additionwas added
2. waitAfter 10 min
3. filtrationThe suspension was filtered
4. concentrationthe filtrate was concentrated under reduced pressure
5. additionwater added
6. customThe aqueous layer was separated
7. extractionextracted three times with dichloromethane
8. dry with materialThe combined organic layers were dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customto give 60 mg of crude product
12. customPurification by column chromatography on silica gel (dichloromethane 1/acetone 1)