Reacción #5499

Ecuación de reacción

trans 3-(acetylthiomethyl)-2-oxo-1-azacyclodecane-10-carboxylic acid

1-hydroxybenzotriazole

4-methylmorpholine

L-hydroxyproline ethyl ester hydrochloride

N-[dimethylaminopropyl]-N'-ethylcarbodiimide hydrochloride

→

N-[[trans 3-(acetylthiomethyl)-2-oxo-1-aza-cyclodecan-10-yl]-carbonyl]-trans 4-hydroxy-L-proline ethyl ester

Disolventes

methylene chloride

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm up to room temperature
2. 2
   Lavadothe organic layer is washed with 1N hydrochloric acid, saturated sodium bicarbonate
3. 3
   Secadodried (MgSO4)
4. 4
   Otrothe solvent is evaporated
5. 5
   OtroThe product is purified by silica gel chromatography (80% ethyl acetate/hexane)

Procedimiento

The enantiomer of trans 3-(acetylthiomethyl)-2-oxo-1-azacyclodecane-10-carboxylic acid of Example 16(0.23 g, 0.80 mmol), 1-hydroxybenzotriazole (0.11 g, 0.80 mmol), 4-methylmorpholine (0.22 mL, 2.0 mmol), and L-hydroxyproline ethyl ester hydrochloride (0.16 g, 0.80 mmol) are dissolved in methylene chloride (5.0 mL), and the reaction is cooled to 0° C. To this solution is added N-[dimethylaminopropyl]-N'-ethylcarbodiimide hydrochloride (0.31 g, 1.60 mmol), and the reaction is allowed to warm up to room temperature and stirred overnight. The reaction is diluted with more methylene chloride, and the organic layer is washed with 1N hydrochloric acid, saturated sodium bicarbonate, dried (MgSO4), and the solvent is evaporated. The product is purified by silica gel chromatography (80% ethyl acetate/hexane) to give N-[[trans 3-(acetylthiomethyl)-2-oxo-1-aza-cyclodecan-10-yl]-carbonyl]-trans 4-hydroxy-L-proline ethyl ester as a single enantiomer, [α]D +5.73° (c=4.1 mg/ml, CH2Cl2) which is assigned the 3R, 10S configuration.

Fuente