反応 #40357

反応方程式

EDCI

Boc-D-Phe-OH

HOBt monohydrate

DIEA

THF

→

Boc-D-Phe-D-Leu-OBn

反応条件

後処理

1. 1
   温度cooled in an ice-water bath
2. 2
   workup.ADDITIONbetween each addition
3. 3
   その他After evaporation of THF
4. 4
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate
5. 5
   洗浄washed sequentially with 10% citric acid, saturated NaHCO3 and water
6. 6
   乾燥The organic phase was dried over sodium sulfate
7. 7
   その他evaporated under reduced pressure
8. 8
   workup.DISSOLUTIONThe residue was dissolved in DCM
9. 9
   洗浄eluted with 20% ethyl acetate in hexanes
10. 10
    その他The eluant was evaporated

実験手順

These syntheses were carried out according to the scheme shown in FIG. 4. The intermediates described below correspond to those shown in FIG. 4. To a suspension of Boc-D-Phe-OH intermediate I-1 (7.96 g, 30.0 mmol), D-Leu-OBn p-TsOH intermediate 1-2 (11.80 g, 30.0 mmol), HOBt monohydrate (4.46 g, 33.0 mmol) and DIEA (8.53 g, 66.0 mmol) in anhydrous THF (250 mL) cooled in an ice-water bath was added EDCI (6.33 g, 33.0 mmol) in four portions over 20 minutes with 5 minutes between each addition. The suspension was stirred overnight from a starting temperature of 0° C. to room temperature. After evaporation of THF, the residue was dissolved in ethyl acetate and washed sequentially with 10% citric acid, saturated NaHCO3 and water. The organic phase was dried over sodium sulfate and evaporated under reduced pressure. The residue was dissolved in DCM, passed through a silica gel plug and eluted with 20% ethyl acetate in hexanes. The eluant was evaporated to give the pure product, Boc-D-Phe-D-Leu-OBn, intermediate 1-3 (12.40 g, 88%) as a clear oil. LC-MS: m/z=469 (M+H).

出典