Water → (2S,4R)-1-Benzyloxycarbonyl-2-(3-ethoxycarbonyl-2-oxopropyl)-4-methoxypyrrolidine

0.5 ml (4.51 mmol) of ethyl bromoacetate were added at 90° C. to a suspension of 57.19 g (875 mmol) of zinc powder in 600 ml of tetrahydrofuran and the resulting reaction mixture was heated under reflux for 1 hour. A solution of 30.00 g (109 mmol) of (2S,4R)-1-benzyloxycarbonyl-2-cyanomethyl-4-methoxypyrrolidine [prepared as described in Preparative Example 1(i)′ above] in 30 ml of tetrahydrofuran and 84.9 ml (766 mmol) of ethyl bromoacetate were added successively to this reaction mixture, and the resulting mixture was then heated under reflux for a further 1.5 hours. After being cooled to room temperature, the reaction mixture was filtrated and the filtrate was concentrated by evaporation under reduced pressure. The residue thus obtained was dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium hydrogencarbonate. The organic extract was washed with water, dried over anhydrous magnesium sulfate and then concentrated by evaporation under reduced pressure. The residue thus obtained was dissolved in a mixture of 200 ml of dioxane and 100 ml of a 1N aqueous solution of hydrochloric acid and then allowed to stand at room temperature for 3 hours. At the end of this time, water was added to the reaction mixture which was then extracted with ethyl acetate. The organic extract was washed with water and then concentrated by evaporation under reduced pressure. The resulting residue was purified by chromatography on a silica gel column using a 2:3 by volume mixture of ethyl acetate and hexane as the eluant to afford 28.23 g (yield: 71%) of the title compound as a pale yellow oil.

1. customthe resulting reaction mixture
2. temperaturewas heated
3. temperatureunder reflux for 1 hour
4. temperaturethe resulting mixture was then heated
5. temperatureunder reflux for a further 1.5 hours
6. filtrationthe reaction mixture was filtrated
7. concentrationthe filtrate was concentrated by evaporation under reduced pressure
8. customThe residue thus obtained
9. washwashed with a saturated aqueous solution of sodium hydrogencarbonate
10. extractionThe organic extract
11. washwas washed with water
12. dry with materialdried over anhydrous magnesium sulfate
13. concentrationconcentrated by evaporation under reduced pressure
14. customThe residue thus obtained
15. extractionwas then extracted with ethyl acetate
16. extractionThe organic extract
17. washwas washed with water
18. concentrationconcentrated by evaporation under reduced pressure
19. customThe resulting residue was purified by chromatography on a silica gel column
20. additionby volume mixture of ethyl acetate and hexane as the eluant

ORD record

ord-1766247480a34c89881f6df12563c8bb

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07122666B2