Реакция #221007

Уравнение реакции

(2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-methyl-3-phenylbutanoic acid

benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate

morpholine

diisopropylethylamine

→

tert-butyl methyl[(1S)-2-methyl-1-(4-morpholinylcarbonyl)-2-phenylpropyl]carbamate

Растворители

dichloromethane

water

dichloromethane

Условия реакции

Обработка

1. 1
   Другоеthe cooling bath is removed
2. 2
   Другоеthe resulting reaction mixture
3. 3
   workup.STIRRINGis stirred at room temperature for 15-20 hours
4. 4
   Экстракцияthe aqueous layer is extracted with ethyl acetate (3 times)
5. 5
   ПромывкаThe combined extracts are washed with saturated sodium chloride solution
6. 6
   Сушкаdried over sodium sulfate
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated in vacuo
9. 9
   ДругоеThe residue is chromatographed (silica gel, flash column)
10. 10
    Другоеto give a dark yellow oil

Методика

To a cooled (0°C., ice bath) solution of (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-methyl-3-phenylbutanoic acid (1.0 g, 3.30 mmol, WO 99/32509) and benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (1.46 g, 3.30 mmol) in anhydrous dichloromethane (5 ml) is added diisopropylethylamine (1.15 ml, 6.60 mmol) under an inert atmosphere. To this solution is added a solution of morpholine (0.313 ml, 3.60 mmol) in dichloromethane (2.5 ml). After stirring at 0° C. for 5-10 minutes, the cooling bath is removed, and the resulting reaction mixture is stirred at room temperature for 15-20 hours. The mixture is diluted with water, and the aqueous layer is extracted with ethyl acetate (3 times). The combined extracts are washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is chromatographed (silica gel, flash column), to give a dark yellow oil. (0.943 g, 76%) MS [M+H] 377.2

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