反应详情

To an ice bath cooled suspension of 2-difluoromethyl-5-hydroxy-pyran-4-one (1.00 g, 6.17 mmol), obtained as described in Example 4, in deionized water was added a 6.0M NaOH solution (1.23 mL, 7.40 mmol). A clear dark brown red solution was obtained, and CH3CHO (6.0 mL, 107 mmol) was added dropwise. After 2 hrs, the reaction mixture was cooled in ice and another 3 mL of CH3CHO (54 mmol) was added. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature overnight. The progress of the reaction was monitored by HPLC Method 1 as described above. Thus, after 24 hrs, the composition (% as peak percent area) of the reaction mixture was as follows: desired product (72%), starting material (7%), side products (15%, 2 major less polar components). The reaction mixture was cooled in ice and the pH was adjusted to 6 with the addition of a 6.0M HCl solution (1 mL). The mixture was concentrated in vacuo, and the residue was taken up in EtOAc. The organic layer was washed with brine (2×15 mL). The combined brine layers were back-extracted with EtOAc (2×). The organic fractions were combined, dried over Na2SO4, filtered, and evaporated to dryness. The residue was purified by column chromatography on silica gel using a mixture of CH2Cl2 and MeOH (25/1, v/v) as eluant. Fractions rich in product were combined together, and concentrated to give 6-difluoromethyl-3-hydroxy-2-(1-hydroxy-ethyl)-pyran-4-one as an oil. HPLC purity (peak area percent) of this material is 88.0% at λ=280 nm using HPLC Method 1 as described above.

1. temperatureTo an ice bath cooled
2. customobtained
3. customA clear dark brown red solution was obtained
4. temperaturethe reaction mixture was cooled in ice
5. customThe cooling bath was removed
6. waitThus, after 24 hrs
7. temperatureThe reaction mixture was cooled in ice
8. additionthe pH was adjusted to 6 with the addition of a 6.0M HCl solution (1 mL)
9. concentrationThe mixture was concentrated in vacuo
10. washThe organic layer was washed with brine (2×15 mL)
11. extractionThe combined brine layers were back-extracted with EtOAc (2×)
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. customevaporated to dryness
15. customThe residue was purified by column chromatography on silica gel using
16. additiona mixture of CH2Cl2 and MeOH (25/1
17. concentrationconcentrated