反应详情

1-[[(2-Carboxyethyl)methylamino]carbonyl]-L-proline, phenylmethyl ester (4.8 g., 15 mmole) is taken into 50 ml. of dry tetrahydrofuran with stirring in an ice bath. To this is added dropwise oxalyl chloride (1.58 ml., 18 mmole) followed by 4 drops of dimethylformamide. After 20 minutes the bath is removed and the reaction is run for one hour at room temperature before concentrating to dryness. This material is taken into 30 ml. of tetrahydrofuran, chilled and added dropwise to 2-phenyl-4-butyl-5(4H)-oxazolone (3.42 g., 15.75 mmole) in 24 ml. of tetrahydrofuran while stirring in an ice bath. Triethylamine (2.55 ml.) is added. After 5 minutes the bath is removed and the reaction is run overnight at room temperature. The triethylamine hydrochlorice salt is filtered off, the filtrate is concentrated to dryness, taken into 16 ml. of pyridine, 50 mg. of 4-dimethylamino pyridine is added, and the mixture is stirred for 3 hours. Acetic acid (16 ml.) is added and the mixture is heated at 100° for 45 minutes. The mixture is concentrated to dryness, taken into ethyl acetate and washed neutral with saturated sodium bicarbonate and dilute hydrochloric acid to give 4.7 g. of product. Purification on silica gel in benzene:ethyl acetate (1:2) yields 1.14 g of (±)-1-[[[3-(benzoylamino)-2-oxoheptyl]methylamino]carbonyl]-L-proline, phenylmethyl ester.

1. customAfter 20 minutes the bath is removed
2. concentrationbefore concentrating to dryness
3. temperatureof tetrahydrofuran, chilled
4. customAfter 5 minutes the bath is removed
5. waitthe reaction is run overnight at room temperature
6. filtrationThe triethylamine hydrochlorice salt is filtered off
7. concentrationthe filtrate is concentrated to dryness
8. additionof 4-dimethylamino pyridine is added
9. additionAcetic acid (16 ml.) is added
10. temperaturethe mixture is heated at 100° for 45 minutes
11. concentrationThe mixture is concentrated to dryness
12. washwashed neutral with saturated sodium bicarbonate and dilute hydrochloric acid
13. customto give 4.7 g
14. customPurification on silica gel in benzene:ethyl acetate (1:2)