反应 #9373

反应方程式

HCl

NaH

dimethylcarbonate

5-fluoroindanone

→

5-fluoro-indan-2-carboxylic acid methyl ester

溶剂

THF

反应条件

后处理

1. 1
   萃取extracted with Et2O or EtOAc
2. 2
   洗涤The organic layers were washed with water
3. 3
   干燥dried over MgSO4
4. 4
   其他evaporated to dryness
5. 5
   其他The residue was used in the next step without further purification
6. 6
   workup.DISSOLUTIONThe keto-ester was dissolved in AcOH (100 mL)
7. 7
   workup.ADDITION10% Pd/C (2 g) was added
8. 8
   workup.ADDITIONThe mixture was diluted with Et2O or CHCl3 and water
9. 9
   过滤filtered through a pad of celite
10. 10
    其他The organic layer was separated
11. 11
    萃取the aqueous layer was extracted with Et2O
12. 12
    洗涤washed with water
13. 13
    干燥dried over MgSO4
14. 14
    过滤filtered
15. 15
    其他evaporated
16. 16
    其他to leave a residue
17. 17
    其他The residue was purified by chromatography on silica gel with 15% EtOAc

实验过程

To a mixture of NaH (2.64 g, 66 mmol) in dimethylcarbonate (4.2 mL, 50 mmol) in THF (30 mL) was added a solution of 5-fluoroindanone (commercially available from Aldrich) (5 g, 33 mmol). After 30 m at 65° C. the mixture was cooled to rt, acidified with HCl (aq) and extracted with Et2O or EtOAc. The organic layers were washed with water, dried over MgSO4 and evaporated to dryness. The residue was used in the next step without further purification. The keto-ester was dissolved in AcOH (100 mL) and 70% perchloric acid (2 mL). 10% Pd/C (2 g) was added and the mixture was hydrogenated at 50 psi for 18 h. The mixture was diluted with Et2O or CHCl3 and water and filtered through a pad of celite. The organic layer was separated and the aqueous layer was extracted with Et2O. The organic fractions were pooled, washed with water, dried over MgSO4, filtered and evaporated to leave a residue. The residue was purified by chromatography on silica gel with 15% EtOAc: hexane to give 5-fluoro-indan-2-carboxylic acid methyl ester (Intermediate EIGHTEEN-3), 2.25 g. Use of 5-fluoro-indan-2-carboxylic acid methyl ester (Intermediate EIGHTEEN-3) in Method SEVENTEEN produced 4-(5-fluoro-indan-2-yl)-1,3-dihydro-imidazole-2-thione (Compound 145).

来源