반응 #220996

반응 방정식

ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate

lithium hydroxide

N-methyl-L-proline monohydrate

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

diisopropylethylamine

→

product

수율 28.0%

1-methyl-L-prolyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide

수율 28.0%

용매

tetrahydrofuran

dichloromethane

methanol

dichloromethane water

water

dichloromethane

반응 조건

후처리

1. 1
   기타The resulting reaction mixture
2. 2
   기타The reaction mixture is evaporated in vacuo
3. 3
   workup.STIRRINGis stirred at room temperature overnight
4. 4
   세척The organic layer is washed with citric acid, brine
5. 5
   건조dried over sodium sulfate
6. 6
   여과filtered
7. 7
   기타The solvent is removed in vacuo
8. 8
   기타the residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile)

실험 절차

To a solution of N-methyl-L-proline monohydrate (0.26 g, 1.79 mmol) and benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (1.4 g, 2.69 mmol) in anhydrous dichloromethane (3.0 ml) at 25° C. is added diisopropylethylamine (0.63 ml, 3.62 mmol) under an inert atmosphere. To this solution is added a solution of ethyl (2E,4S)-2,5-dimethyl-4-[methyl(3-methyl-L-valyl)amino]hex-2-enoate (0.39 g, 1.27 mmol, WO 99/32509) in anhydrous dichloromethane (2.0 ml). The resulting reaction mixture is stirred at room temperature overnight. The reaction mixture is evaporated in vacuo. The residue (300 mg, 0.78 mmol) is dissolved in methanol (6.85 ml), water (1.8 ml) and tetrahydrofuran (3.25 ml). To this reaction mixture is added aqueous lithium hydroxide solution (3.54 ml, 3.54 mol) The resulting mixture is stirred at room temperature overnight. The reaction mixture is diluted with dichloromethane/water. The organic layer is washed with citric acid, brine, dried over sodium sulfate and filtered. The solvent is removed in vacuo, and the residue is chromatographed by HPLC (0.01% trifluoroacetic acid in water/acetonitrile) to give the product as a yellow oil, 0.08 g (28% yield). MS: m/z 396.28 (M+1)

출처