Acetyl chloride → N-(4-methoxycarbonyl-2-methylbutanoyl)-L-alanine benzyl ester

2-Methylglutaric acid (14.6 g.) and acetyl chloride (26 ml.) are heated in the steam bath for one hour. The mixture is concentrated to dryness in vacuo and the residue is evaporated twice from toluene. The residue is dissolved in methanol (4.7 ml.) and heated on the steam bath for one hour and concentrated to dryness. The residue is dissolved in a mixture of ether (17 ml.), dicyclohexylamine (16.7 ml.) and hexane (83 ml.). The crystalline salt is filtered off and the filtrate is concentrated to one third volume and chilled. The crystals are filtered and dried to yield 11.3 g. of 4-methoxycarbonyl-2-methyl butanoic acid dicyclohexylamine salt, m.p. 97°-99°. The salt is converted to the free acid by distribution between ethyl acetate and aqueous acid. (b) 4-methoxycarbonyl-2-methylbutanoic acid (3.1 g.), L-alanine benzyl ester (3.58 g.) and hydroxybenzotriazole (2.7 g.) are dissolved in dichloromethane. The solution is chilled in the ice bath and dicyclohexylcarbodiimide (4.12 g.) is added. After stirring 15 minutes in the ice bath and 18 hours at room temperature the precipitate is filtered off and the filtrate is concentrated to dryness. The residue is dissolved in ethyl acetate and washed neutral. The organic phase is dried over magnesium sulfate and concentrated to dryness to yield N-(4-methoxycarbonyl-2-methylbutanoyl)-L-alanine benzyl ester.

1. concentrationThe mixture is concentrated to dryness in vacuo
2. customthe residue is evaporated twice from toluene
3. dissolutionThe residue is dissolved in methanol (4.7 ml.)
4. temperatureheated on the steam bath for one hour
5. concentrationconcentrated to dryness
6. dissolutionThe residue is dissolved in a mixture of ether (17 ml.), dicyclohexylamine (16.7 ml.) and hexane (83 ml.)
7. filtrationThe crystalline salt is filtered off
8. concentrationthe filtrate is concentrated to one third volume
9. temperaturechilled
10. filtrationThe crystals are filtered
11. customdried
12. customto yield 11.3 g
13. additionis added
14. filtrationis filtered off
15. concentrationthe filtrate is concentrated to dryness
16. dissolutionThe residue is dissolved in ethyl acetate
17. washwashed neutral
18. dry with materialThe organic phase is dried over magnesium sulfate
19. concentrationconcentrated to dryness

ORD record

ord-497f51e961ed47e6ac2f683e3a104a1b

Source dataset

uspto-grants-1980_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04228184