Diazomethane → Methyl 7-[5-((1E)(3S)-3-hydroxyoct-1-enyl)(1R,4R,5R)-4-hydroxy-2-oxocyclopentyl]heptanoate

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

7-[5-((1E)(3S)-3-hydroxyoct-1-enyl)(1R,4R,5R)-4-(hydroxy-2-oxocyclopentyl)heptanoic acid (311 mg, 0.877 mmol) was slurried in diethyl ether (10 mL) in a 50 mL erlenmeyer flask and cooled to 0° C. In a separate 50 mL erlenmeyer flask, N-methyl-N-nitrosourea (271 mg, 2.63 mmol, 3 eq) was added to a 1:1 mix of water/diethyl ether (20 mL) and cooled to 0° C. KOH was added to the N-methyl-N-nitrosourea mix at 0° C., generating diazomethane as evidenced by the formation of a yellow color in the diethyl ether layer. After 5 minutes, the yellow ethereal diazomethane solution was slowly added to the prostaglandin solution via a flame polished pipette slowly resulting in the dissolution of the solid material. Once the prostaglandin had gone into solution and a yellow color was maintained in the reaction mixture, addition of the ethereal diazomethane was stopped and both mixtures were allowed to slowly warm to ambient temperature and left until all the yellow color had disappeared. The prostaglandin reaction mixture was dried over sodium sulfate and then the solvent was concentrated in vacuo to give the title compound as a clear colorless oil (99.5%): 1H NMR (300 MHz, CDCl3) δ 5.63 (dd, 1H, J=15.3, 6.8 Hz), 5.49 (dd, 1H, J=15.3, 8.5 Hz), 4.02 (m, 2H), 3.59 (s, 3H), 2.42 (AB part of ABX, 2H, JAB=18.4 Hz, JAX=9.8 Hz, JBX=6.6 Hz, ΔνAB=8.2 Hz), 2.29 (dt, 1H, J=12.0, 8.6 Hz), 2.22 (t, 2H, J=7.4 Hz), 1.94 (m, 1H), 1.80-1.15 (m, 18H), 0.82 (t, 3H, J=6.5 Hz).

Herkunft & Nachweise