反応 #57015

反応方程式

HCl

NaH

dimethylcarbonate

5-fluoroindanone

→

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

溶媒

THF

反応条件

後処理

1. 1
   抽出extracted with Et2O or EtOAc
2. 2
   洗浄The organic layers were washed with water
3. 3
   乾燥dried over MgSO4
4. 4
   その他evaporated to dryness
5. 5
   その他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
   ろ過filtered through a pad of celite
10. 10
    その他The organic layer was separated
11. 11
    抽出the aqueous layer was extracted with Et2O
12. 12
    洗浄washed with water
13. 13
    乾燥dried over MgSO4
14. 14
    ろ過filtered
15. 15
    その他evaporated
16. 16
    その他to leave a residue
17. 17
    その他The residue was purified by chromatography on silica gel with 15% EtOAc

実験手順

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).

出典