HCID 88831128, compound → HCID 178506905, compound

Temperature

-78 °C

2.50 g (8.40 mmol) of trans-4-methyl-3α-ethoxyethoxy-1 -iodopentene was dissolved in 57 ml of anhydrous ether and cooled to -78° C. with stirring under argon atmosphere. To this solution 13.7 ml of 1.23 N t-butyllithium in pentane was injected. The resulting solution was stirred for 2.75 hours at -78° C. under argon atmosphere, yielding the lithio-anion, 1-lithio-trans-4-methyl-3α-ethoxyethoxy-1-pentene. The lithio-anion was added to a solution of 0.44 g hexamethylenephosphorous triamide copper iodide in 50 ml of anhydrous ether at -78° C. under argon. This yellow mixture was stirred for 15 minutes at -78° C. Then 1.97 g (4.22 mmol) of 15α-ethoxyethoxy-PGA2 -methyl ester in 11.5 ml ether was added dropwise and the reaction mixture was stirred at -70° C. for 15 min. The mixture was then slowly warmed to 0° C. over a period of 1.5 hr. by use of an ice water and salt bath, and stirred for 0.5 hr. The mixture was then brought to 25° C. and stirred for an additional 0.5 hr. The mixture was then processed with a 20% aqueous NH4Cl/NH4OH solution and 3.35 g of an orange oil was obtained. NMR(CDCl3) analysis revealed: δ 3.65, singlet, CO2CH3 ; δ Ξ5.45, multiplet, olefinic-H; and no absorption due to olefinic protons on the cyclopen-tenone in the PGA2 starting material. The ethoxyethoxy groups were hydrolyzed by reacting with 70 ml of 65/35 acetic acid/water and 7.0 ml THF for 17 hours at 25° C. After processing, 3.30 g of an orange oil were obtained. NMR (CDCl3) analysis showed no absorption in the δ 4.80 region. The methyl ester was hydrolyzed by reaction with 22 ml of 1N NaOH and 22 ml of THF for 19 hours at 25° C. under argon atmosphere. After processing 3.28 g of a red oil was obtained chromatographed in Silicic Acid and Celite (15%). 1.227 g (65.6%) of (-)-11α-(trans-4'-methyl-3'-β -hydroxy-1-pentenyl-11 -desoxy-PGE2 was obtained. NMR(CDCl3) analysis: δ 3.95, multiplet, 2H, CHOH; δ 5.45, multiplet, 6H, CO2H, -OH. IR analysis: λmaxCHCl3 2.68μ5.75μ, 5.85μ. Optical rotation: [α]D 25° = 36.4 ± 02° (c = 1.0, CH3OH). Mass spectoscopy: 416 (P+ - 18).

1. stirringThe resulting solution was stirred for 2.75 hours at -78° C. under argon atmosphere

ORD record

ord-9540e31e0d4448d6ba1516701e019881

Source dataset

uspto-grants-1976_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US03989744