Dimethylformamide → 2-allyl-5-aminopentanoic Acid

Diethyl allylmalonate was slowly added into a suspension of 1.1 eq. sodium hydride in DMF and stirred at RT for 5 minutes after addition. Then N-(3-bromopropyl)-phthalimide dissolved in DMF was added and the reaction mixture were stirred at 60° C. overnight. The solution was then slowly poured into 3 volumes of ice-water; alkylation product 2 precipitated, and the precipitate was collected by filtration. The filter cake was washed with water. HPLC analysis demonstrated that 2 was pure enough for use in the next step without further purification. Attempts to deprotect and decarboxylate 2 by refluxing in 6 M HCl did not yield the desired product. Instead, decarboxylation of 2 was achieved by refluxing in DMF with 1 eq of lithium bromide and 2 eq. of water for 40 hrs to yield desired intermediate 3. Compound 3 was converted into 4 by refluxing for 1 hr with 2 eq. NaOH (1M aq) in DMF, then 1 hr in water. After removing volatiles under vacuum, the residue was treated with 5 eq. of hydrazine, suspended in absolute ethanol, and refluxed overnight. Upon cooling, most of the liberated phthalhydrazide precipitated out; the precipitate was removed by filtration. After filtration, 2 eq. LiOH was added to the filtrate and the solvent was evaporated to afford crude 1 as its lithium salt. This was used directly for solid phase synthesis.

1. additionafter addition
2. additionwas added
3. stirringthe reaction mixture were stirred at 60° C. overnight
4. customalkylation product 2 precipitated
5. filtrationthe precipitate was collected by filtration
6. washThe filter cake was washed with water
7. customwas pure enough for use in the next step without further purification
8. temperatureby refluxing in 6 M HCl

ORD record

ord-0b6ca5105c3a4e89b531d3cfe9f195b2

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06753449B2