반응 #57015

반응 방정식

HCl

NaH

dimethylcarbonate

5-fluoroindanone

→

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

용매

THF

반응 조건

후처리

1. 1
   추출extracted with Et2O or EtOAc
2. 2
   세척The organic layers were washed with water
3. 3
   건조dried over MgSO4
4. 4
   기타evaporated to dryness
5. 5
   기타The 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
   여과filtered through a pad of celite
10. 10
    기타The organic layer was separated
11. 11
    추출the aqueous layer was extracted with Et2O
12. 12
    세척washed with water
13. 13
    건조dried over MgSO4
14. 14
    여과filtered
15. 15
    기타evaporated
16. 16
    기타to leave a residue
17. 17
    기타The residue was purified by chromatography on silica gel with 15% EtOAc

실험 절차

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).

출처