Reacción #220996

Ecuación de reacción

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

Rendimiento 28.0%

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

Rendimiento 28.0%

Disolventes

tetrahydrofuran

dichloromethane

methanol

dichloromethane water

water

dichloromethane

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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)

Fuente