Triethylamine → {2-[(2-Cyano-ethylcarbamoyl)-methyl]-4-methyl-pentyl}-carbamic acid tert-butyl ester

Temperatur

0 °C

A solution of compound 2 (8.0 g, 0.03 mol) (prepared in the usual manner from (BOC)2 and pregabalin) was taken up in 250 mL dry THF and cooled in an ice water bath. Triethyl amine (4.62 mL, 0.033 mol) was added followed by the addition of isobutyle chloroformate (4 mL, 0.031 mol). The reaction was stirred at 0° C. for about 15 minutes during which time a precipitate formed. In a separate flask was placed 3-aminoproprionitrile fumarate (3.95 g, 0.03 mol) in 35 mL of 1 M NaOH and 300 mL of THF. This mixture was cooled to 0° C. and treated with the mixed anhydride formed above in four portions. Before each portion was added, 35 mL of 1 M NaOH was added to the mixture. The reaction was stirred for 24 hours and was then concentrated to remove THF. The resulting aqueous was extracted with three times ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate. The solvents were removed under reduced pressure to give 6.6 g green oil. MS(APCI) m/z 312 (M+1).

1. temperaturecooled in an ice water bath
2. customformed
3. customIn a separate flask was placed
4. temperatureThis mixture was cooled to 0° C.
5. customformed above in four portions
6. additionBefore each portion was added
7. stirringThe reaction was stirred for 24 hours
8. concentrationwas then concentrated
9. customto remove THF
10. extractionThe resulting aqueous was extracted with three times ethyl acetate
11. washThe combined organic extracts were washed with brine
12. dry with materialdried over magnesium sulfate
13. customThe solvents were removed under reduced pressure

ORD-Eintrag

ord-ca88aac57b4944b58ac28bd53772273e

Quelldatensatz

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06521650B1