Water → 3-Propylpiperidin-2-one

To delta-valerolactam (10 g) dissolved in 80 ml of dry tetrahydrofuran, under a dry nitrogen atmosphere was deopwise added n-butyllithium (1.6M, 125 ml) in hexane while the reaction mixture was chilled in a dry ice-acetone bath. After all the n-butyllithium was added, the reaction mixture was stirred at room temperature for one hour, refluxed for thirty minutes, and cooled to room temperature. 1-Bromopropane (12.3 g) was slowly added to the reaction mixture while the mixture was chilled in an ice bath. The reaction mixture was then stirred for sixteen hours at room temperature. 100 ml of water was added slowly to the reaction mixture and the resulting mixture was stirred at room temperature for thirty minutes. The layers separated and the aqueous layers were combined, dried over sodium sulfate, and then evaporated to yield 12.4 g (88% yield) of a dark, heavy oil, which crystallized on standing. The crystals were recrystallized from petroleum ether to yield 5.4 g of α-propylvalerolactam (m.p. 75°-76° C.). A portion of the α-propylvalerolactam (2.8 g) was refluxed in 25 ml of 6N hydrochloric acid under a nitrogen atmosphere for six hours. The water was evaporated to yield 2-propyl-5-amino-pentanoic acid (2.0 g; 51% yield) and recrystallized from ethanol-petroleum ether to yield a solid (m.p. 71°-73° C.). Equimolar amounts of 2-propyl-5-amino-pentanoic acid and 5-[(4,6-dichlorotriazin-2-yl)-amino]fluorescein were dissolved in methanol. The reaction was completed in about ten minutes to yield a crude product which was purified by silica gel thin-layer chromatography with chloroform/methanol (3:1) as the developing solvent to yield a 2-propyl-5-amino-pentanoic acid-DTAF conjugate of the formula: ##STR11##

1. temperaturewas chilled in a dry ice-acetone bath
2. temperaturerefluxed for thirty minutes
3. temperaturecooled to room temperature
4. temperaturewas chilled in an ice bath
5. stirringThe reaction mixture was then stirred for sixteen hours at room temperature
6. stirringthe resulting mixture was stirred at room temperature for thirty minutes
7. customThe layers separated
8. dry with materialdried over sodium sulfate
9. customevaporated
10. customto yield 12.4 g (88% yield) of a dark, heavy oil, which
11. customcrystallized
12. customThe crystals were recrystallized from petroleum ether

ORD record

ord-982c4879c0d548dab58d0a1ebf64a228

Source dataset

uspto-grants-1986_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04593089