反应 #42359

反应方程式

diisopropylethylamine

(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride

HATU

Methyl 3-{4-[2-(benzyloxy)ethyl]-1,3-oxazol-2-yl}benzoate

cyclohexene

lithium hydroxide

→

title compound

N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-[4-(2-hydroxyethyl)-1,3-oxazol-2-yl]benzamide

溶剂

chloroform

ethanol

反应条件

后处理

1. 1
   温度The reaction is cooled
2. 2
   过滤filtered through diatomaceous earth
3. 3
   浓缩concentrated under reduced pressure
4. 4
   workup.DISSOLUTIONThe residue is redissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL)
5. 5
   浓缩concentrated under reduced pressure
6. 6
   workup.DISSOLUTIONThe residue is dissolved in DMF (5 mL)
7. 7
   workup.ADDITIONare added
8. 8
   workup.STIRRINGThe reaction stirred at room temperature 16 h
9. 9
   洗涤washed with water, 1N hydrochloric acid (aq), saturated sodium bicarbonate, brine
10. 10
    干燥dried (sodium sulfate)
11. 11
    过滤filtered
12. 12
    浓缩concentrated under reduced pressure
13. 13
    其他Purification by flash column chromatography (silica, 8% methanol/chloroform)

实验过程

Methyl 3-{4-[2-(benzyloxy)ethyl]-1,3-oxazol-2-yl}benzoate (300 mg, 0.9 mmol), 20% palladium(II) hydroxide on carbon (65 mg), and cyclohexene (3 mL) in absolute ethanol (3 mL) are refluxed 1 h. The reaction is cooled, filtered through diatomaceous earth, and concentrated under reduced pressure. The residue is redissolved in 2:1:1 tetrahydrofuran/methanol/water (4 mL) is added lithium hydroxide (75 mg, 1.8 mmol). The reaction mixture is stirred at room temperature for 3 h, and concentrated under reduced pressure. The residue is dissolved in DMF (5 mL), and diisopropylethylamine (625 μL, 3.6 mmol), HATU (540 mg, 1.4 mmol), and (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method in Example SP-272 (407 mg, 1 mmol) are added. The reaction stirred at room temperature 16 h. The reaction mixture is diluted with chloroform, washed with water, 1N hydrochloric acid (aq), saturated sodium bicarbonate, brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 8% methanol/chloroform) provides the title compound. ESI MS m/z 550.3 [M+H]+.

来源