Reacción #89715

Ecuación de reacción

dry ice acetone

water

(S)-2-benzylamino-succinic acid 1-benzyl ester 4-methyl ester

(2S)-(+)-glycidyl tosylate

trimethylaluminum

sodium fluoride

→

titled compound

Rendimiento 91.8%

1-benzyl 4-methyl(2S)-2-[benzyl((2S)-2-hydroxy-3-[(4-methylphenyl)sulfonyl]oxypropyl)amino]succinate

Rendimiento 91.8%

Disolventes

methylene chloride

methylene chloride

toluene

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe resulting reaction mixture
2. 2
   workup.STIRRINGwas stirred at −78 Celsius for 30 min
3. 3
   Temperaturato warm the mixture up to 0 Celsius
4. 4
   workup.STIRRINGThe mixture was stirred at 0 Celsius for 30 min
5. 5
   workup.STIRRINGThe resulting suspension was rapidly stirred for 1 h at 0 Celsius
6. 6
   Filtraciónfiltered through a short column of of celite
7. 7
   Lavadothe column was subsequently washed with 600 mL of methylene chloride
8. 8
   SecadoThe combined filtrates were dried over sodium sulfate
9. 9
   Concentraciónconcentrated
10. 10
    Otroto dry
11. 11
    Otropurified by column purification (eluting with 0 to 20% EtOAc in hexane)

Procedimiento

To a solution of (2S)-(+)-glycidyl tosylate (23.0 g, 0.101 mol) in 500 mL of methylene chloride was added 2.00 M of trimethylaluminum in toluene (50.4 mL) at −78 Celsius, under an atmosphere of nitrogen. After stirred at −78 Celsius for 10 min, to the mixture was added a solution of (S)-2-benzylamino-succinic acid 1-benzyl ester 4-methyl ester (30.0 g, 0.0916 mol) in 150 mL of methylene chloride. The resulting reaction mixture was stirred at −78 Celsius for 30 min. The dry ice-acetone bath was changed to an ice-water bath to warm the mixture up to 0 Celsius. The mixture was stirred at 0 Celsius for 30 min. To the reaction mixture was added sodium fluoride (16.2 g, 0.385 mol) followed by water (10.4 mL, 0.577 mol) at 0 Celsius. The resulting suspension was rapidly stirred for 1 h at 0 Celsius and filtered through a short column of of celite and the column was subsequently washed with 600 mL of methylene chloride. The combined filtrates were dried over sodium sulfate, concentrated to dry and purified by column purification (eluting with 0 to 20% EtOAc in hexane) to yield The titled compound (46.7 g, 91.7%). MS (ESI): (M+H)+=556.2.

Fuente