反応 #550078

反応方程式

N-methylmorpholine

NaH

isobutylchloroformate

Boc-Pro-OH

Boc-Pro-OH

Ethyl fluoroacetate

→

oil

2-(2'-Ethoxycarbonyl-2'-fluoroacetyl)-N-t-butoxycarbonylpyrrolidine

溶媒

ether

THF

ether

反応条件

後処理

1. 1
   温度cooled to -15°
2. 2
   workup.STIRRINGstirred 5 minutes]
3. 3
   ろ過was filtered into the chilled enolate suspension
4. 4
   workup.STIRRINGstirred at -15° for 10 minutes
5. 5
   温度to warm to room temperature for one hour
6. 6
   workup.ADDITIONThe solution was poured onto ice containing 2.5N H2SO4
7. 7
   その他The organic solvents were removed by evaporation
8. 8
   抽出the aqueous residue extracted with ethyl acetate
9. 9
   洗浄The ethyl acetate solution was washed with saturated NaHCO3, saturated with NaCl
10. 10
    乾燥dried over anhydrous MgSO4
11. 11
    その他The ethyl acetate was removed by evaporation
12. 12
    洗浄The product was eluted with chloroform
13. 13
    その他The solvent was removed by evaporation

実験手順

Ethyl fluoroacetate (2.0 g, 18.9 m mol) in ether (25 ml) was added dropwise with stirring to a suspension of NaH (50 percent oil dispersion)(0.91 g, 18.9 m mol) in ether (20 ml). The reaction mixture was stirred three hours at room temperature, then cooled to -15°. The mixed anhydride of Boc-Pro-OH [prepared from Boc-Pro-OH (4.1 g, 18.9 m mol) in the THF (50 ml) containing N-methylmorpholine (2.1 ml, 18.9 m mol) at -15°, by the addition of isobutylchloroformate (2.45 ml, 18.9 m mol) and stirred 5 minutes] was filtered into the chilled enolate suspension and stirred at -15° for 10 minutes. The reaction was then allowed to warm to room temperature for one hour. The solution was poured onto ice containing 2.5N H2SO4. The organic solvents were removed by evaporation and the aqueous residue extracted with ethyl acetate. The ethyl acetate solution was washed with saturated NaHCO3, saturated with NaCl, and dried over anhydrous MgSO4. The ethyl acetate was removed by evaporation and the residue was applied to a silica gel column. The product was eluted with chloroform. The solvent was removed by evaporation yielding 1.08 g of an oil. The 1H nmr (CDCl3) showed peaks shifted from TMS by ##STR5##

出典