反应 #367379

反应方程式

3-[2-chloro-5-(methylsulfonyl)-3-pyridinyl]-1-(3,4-dichlorophenyl)propan-1-one

diisobutylaluminum hydride toluene

→

2-(3,4-dichlorophenyl)-3,4-dihydro-6-(methylsulfonyl)-2H-pyrano[2,3-b]pyridine

溶剂

methylene chloride

反应条件

后处理

1. 1
   其他the temperature below -65° C
2. 2
   其他the mixture was quenched by careful addition of 1.5 ml of a mixture
3. 3
   其他was partitioned between water and methylene chloride
4. 4
   洗涤The methylene chloride layer was washed with aqueous saturated sodium bicarbonate solution
5. 5
   干燥dried over magnesium sulfate
6. 6
   过滤filtered
7. 7
   浓缩the filtrate was concentrated to a colorless solid, 3-[2-chloro-5-(methylsulfonyl)-3-pyridinyl]-1-(3,4-dichlorophenyl)propan-1-ol
8. 8
   workup.DISSOLUTIONThis solid was dissolved in 2 ml of anhydrous dimethyl sulfoxide
9. 9
   workup.ADDITIONadded to a stirred suspension of 0.07 g of 50% sodium hydride (
10. 10
    洗涤by washing with hexane) in 10 ml of dimethyl sulfoxide under nitrogen
11. 11
    workup.WAITAfter 15 minutes
12. 12
    其他it was partitioned between ethyl acetate and 1N hydrochloric acid
13. 13
    洗涤The yellow ethyl acetate layer was washed with water
14. 14
    干燥twice with aqueous saturated sodium chloride solution, dried over magnesium sulfate
15. 15
    过滤filtered
16. 16
    浓缩the filtrate was concentrated
17. 17
    其他to leave a pale yellow solid
18. 18
    其他This solid was recrystallized from a mixture of 2-propanol and ethyl acetate

实验过程

A solution of 0.39 g of 3-[2-chloro-5-(methylsulfonyl)-3-pyridinyl]-1-(3,4-dichlorophenyl)propan-1-one in 15 ml of methylene chloride was cooled to -70° C. under nitrogen and then a solution of 1.0 ml of 1.5M diisobutylaluminum hydride/toluene was added dropwise over 3 minutes while keeping the temperature below -65° C. After an additional 5 minutes, the mixture was quenched by careful addition of 1.5 ml of a mixture consisting of 10% water, 40% acetic acid and 50% ether. The reaction mixture was then allowed to warm to 0° C. and was partitioned between water and methylene chloride. The methylene chloride layer was washed with aqueous saturated sodium bicarbonate solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated to a colorless solid, 3-[2-chloro-5-(methylsulfonyl)-3-pyridinyl]-1-(3,4-dichlorophenyl)propan-1-ol. This solid was dissolved in 2 ml of anhydrous dimethyl sulfoxide and added to a stirred suspension of 0.07 g of 50% sodium hydride (previously freed of oil by washing with hexane) in 10 ml of dimethyl sulfoxide under nitrogen. Gas evolution took place and the mixture first became lavender and then cherry red. After 15 minutes, it was partitioned between ethyl acetate and 1N hydrochloric acid. The yellow ethyl acetate layer was washed with water and then twice with aqueous saturated sodium chloride solution, dried over magnesium sulfate and filtered and the filtrate was concentrated to leave a pale yellow solid. This solid was recrystallized from a mixture of 2-propanol and ethyl acetate to give 2-(3,4-dichlorophenyl)-3,4-dihydro-6-(methylsulfonyl)-2H-pyrano[2,3-b]pyridine melting at about 171.5°-172.5° C. This material exhibited the same spectral characteristics as the material prepared by the procedure described in Example 17. This compound has the following structural formula: ##STR7##

来源