反应详情

Water free LiCl (59.4 g, 1.4 mol) is carefully dried in vacuo at 600° for 10 minutes and then the vessel purged with Ar. THF (460 ml) is added and cooled to 0°. A solution of LDA (2M in THF/heptane/Et2O, 200 ml, 0.4 mol) is added and cooled to −75°. A solution of N-[(1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl]-N-methyl-propionamide (44.4 g, 0.2 mol) in 460 ml THF is added dropwise over 170 minutes while maintaining the internal temperature at −62° to −69°. After stirring for 1 h at −75°, the cooling bath is removed for 30 minutes, during which time the temperature rises to −30°. The mixture is recooled to −75° and then treated with a solution of 5-bromomethyl-benzo[1,2,5]thiadiazole (34.8 g, 0.152 mol) in 260 ml THF during 85 min at −70° to −78°. The mixture is then stirred for 40 h at −78°. A 15% NH4Cl solution (1000 ml) is added and the mixture stirred well. Extraction with EtOAc (2×500 ml), drying (Na2SO4) and evaporation afford crude product. MPLC purification (2 kg silicagel, EtOAc/hexanes 2/1) afford pure product as a orange oil. Diastereomeric ration 92:8 (NMR, 120°). TLC (silicagel, EtOAc/hexanes2:1): rf 0.38.

1. customthe vessel purged with Ar
2. additionTHF (460 ml) is added
3. temperaturecooled to 0°
4. temperaturecooled to −75°
5. temperaturewhile maintaining the internal temperature at −62° to −69°
6. customthe cooling bath is removed for 30 minutes, during which time the temperature
7. customrises to −30°
8. customis recooled to −75°
9. stirringThe mixture is then stirred for 40 h at −78°
10. stirringthe mixture stirred well
11. extractionExtraction with EtOAc (2×500 ml)
12. customdrying
13. custom(Na2SO4) and evaporation
14. customafford crude product
15. customMPLC purification (2 kg silicagel, EtOAc/hexanes 2/1)
16. customafford pure product as a orange oil