Water → (S)-1-((S)-2-((Methoxycarbonyl)amino)-3-methylbutanoyl)pyrrolidine-2-carboxylic acid

To a mixture of L-proline (4.44 g, 38.6 mmol), water (20 ml), acetonitrile (20 ml) and DIEA (9.5 g, 73.5 mmol) was added a solution of the product from Example 37A (10 g, 36.7 mmol) in acetonitrile (20 mL) over 10 minutes. The reaction mixture was stirred overnight at room temperature. The solution was concentrated under vacuum to remove the acetonitrile. To the resulting clear water solution was added 6N HCl (9 ml) until pH˜2. The solution was transferred to a separatory funnel and 25% NaCl (10 ml) was added and the mixture was extracted with ethyl acetate (75 ml), and then again with ethyl acetate (6×20 ml), and the combined extracts were washed with 25% NaCl (2×10 ml). The solvent was evaporated to give a thick oil. Heptane was added and the solvent was evaporated to give a foam, which was dried under high vacuum. Diethyl ether was added and the solvent was evaporated to give a foam, which was dried under high vacuum to give the title compound (10.67 g) as a white solid.

1. concentrationThe solution was concentrated under vacuum
2. customto remove the acetonitrile
3. additionTo the resulting clear water solution was added 6N HCl (9 ml) until pH˜2
4. customThe solution was transferred to a separatory funnel
5. addition25% NaCl (10 ml) was added
6. extractionthe mixture was extracted with ethyl acetate (75 ml)
7. washagain with ethyl acetate (6×20 ml), and the combined extracts were washed with 25% NaCl (2×10 ml)
8. customThe solvent was evaporated
9. customto give a thick oil
10. customthe solvent was evaporated
11. customto give a foam, which
12. customwas dried under high vacuum
13. additionDiethyl ether was added
14. customthe solvent was evaporated
15. customto give a foam, which
16. customwas dried under high vacuum

ORD-Eintrag

ord-0a486ae94a8942229c3ef19cc3cedab2

Quelldatensatz

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09006387B2