Reaktion #42043

Reaktionsgleichung

ethyl 4-(bromomethyl)-3-trifluoromethylbenzoate

(S)-3-(t-butoxycarbonylamino)pyrrolidin-2-one

sodium hydride

→

objective compound

ethyl 4-[(S)-3-(t-butoxycarbonylamino)-2-oxopyrrolidin-1-ylmethyl]-3-trifluoromethylbenzoate

Lösungsmittel

tetrahydrofuran

tetrahydrofuran N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture was stirred for 20 minutes
2. 2
   workup.STIRRINGby stirring at room temperature for 6 hours
3. 3
   Sonstigeafter removing an ice bath
4. 4
   workup.ADDITIONThe reaction solution was poured into an aqueous saturated ammonium chloride solution
5. 5
   Extraktionfollowed by extraction with ethyl acetate twice
6. 6
   Trocknendried over anhydrous magnesium sulfate
7. 7
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
8. 8
   SonstigeThe residue was purified by silica gel column chromatography

Vorschrift

669 mg of (S)-3-(t-butoxycarbonylamino)pyrrolidin-2-one (J. Med. Chem., 1999, 42, 3557-3571) was dissolved in 30 ml of tetrahydrofuran/N,N-dimethylformamide (9:1) and the mixture was stirred under ice cooling. 60% sodium hydride was added thereto and the mixture was stirred for 20 minutes. A solution (3 ml) of ethyl 4-(bromomethyl)-3-trifluoromethylbenzoate (Reference Example 2 (step 2)) in tetrahydrofuran was added dropwise, followed by stirring at room temperature for 6 hours after removing an ice bath. The reaction solution was poured into an aqueous saturated ammonium chloride solution, followed by extraction with ethyl acetate twice, and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 867 mg of the objective compound as pale yellow crystals.

Quelle