Réaction #89715

Équation de réaction

dry ice acetone

water

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

(2S)-(+)-glycidyl tosylate

trimethylaluminum

sodium fluoride

→

titled compound

Rendement 91.8%

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

Rendement 91.8%

Solvants

methylene chloride

methylene chloride

toluene

Conditions de réaction

Traitement

1. 1
   AutreThe resulting reaction mixture
2. 2
   workup.STIRRINGwas stirred at −78 Celsius for 30 min
3. 3
   Températureto 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
   Filtrationfiltered through a short column of of celite
7. 7
   Lavagethe column was subsequently washed with 600 mL of methylene chloride
8. 8
   SéchageThe combined filtrates were dried over sodium sulfate
9. 9
   Concentrationconcentrated
10. 10
    Autreto dry
11. 11
    Autrepurified by column purification (eluting with 0 to 20% EtOAc in hexane)

Mode opératoire

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.

Source