反応 #89715

反応方程式

dry ice acetone

water

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

(2S)-(+)-glycidyl tosylate

trimethylaluminum

sodium fluoride

→

titled compound

収率 91.8%

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

収率 91.8%

溶媒

methylene chloride

methylene chloride

toluene

反応条件

後処理

1. 1
   その他The resulting reaction mixture
2. 2
   workup.STIRRINGwas stirred at −78 Celsius for 30 min
3. 3
   温度to 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
   ろ過filtered through a short column of of celite
7. 7
   洗浄the column was subsequently washed with 600 mL of methylene chloride
8. 8
   乾燥The combined filtrates were dried over sodium sulfate
9. 9
   濃縮concentrated
10. 10
    その他to dry
11. 11
    その他purified by column purification (eluting with 0 to 20% EtOAc in hexane)

実験手順

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.

出典