Hydrolysis of the vinyl ether functional group in a model for prostacyclin in which the carboxyl group has been replaced by a pyridine ring

Investigations into a mild Diels-Alder approach to 6-substituted quinazoline-2,4-dione derivatives

“…The reaction was worked up as described for 3a and 4a to give a mixture of 3b and 4b as an oil, 2.5 g (77%). The products were separated by flash chromatography using 1 % methanol in methylene chloride as the eluant to give the product, 3b, which was crystallized from ether/hexane as a colorless solid, 0.91 g (28%): mp 115-117 °C; IR 1736.1704.1664, and 1500 cm"1; MS m/z 471 (MH+); >H NMR (CDC13) 8 1.86 (dd, J = 12.2 and 3.9 Hz, 1 H), 2.27-2.36 (m, 1 H), 2.53-2.82 (m, 6 H), 3.00-3.49 (m, 4 H), 3.33-3.38 (m, 1 H), 3.43 (s, 3 H), 3.62 (s, 3 H), 3.85 (s, 3 H), 4.01-4.17 (m, 2 H), 5.33 (d, J = 4.8 Hz, 1 H), 5.60 Anal. Calcd for C^HaoNAVzHA C, 60.11; H, 6.51; N, 11.68.…”

“…The reaction was worked up as for 3a and 4a to give a mixture of Diels-Alder adducts (Table I, entry 4), 2.88 g (81%). The 6-endo product was isolated by medium-pressure chromatography, using 1% methanol in methylene chloride as the eluant, to give a colorless solid 1.9 g (54%): mp 146-148 °C; IR 2816, 1707,1664,1650, and 1500 cm'1; MS m/z 455 (MH+); 'H NMR (CDC13) 8 1.98 (dd, J = 3.9 Hz and J = 12.1 Hz, 1 H), 2.08-2.17 (m, 1 H), 2.31 (s, 3 H), 2.59 (m, 2 H), 2.73 (m, 4 H), 3.07 (m, 4 H), 3.42 (s, 3 H), 3.43-3.55 (m, 1 H), 3.85 (s, 3 H), 4.01-4.11 (m, 2 H), 5.30 (d, J = 5.2 Hz, 1 H), 5.68 (d, J = 4.1 Hz, 1 H), and I, Entry 9, Endo).…”

“…The product was extracted into 5% isopropanol in methylene chloride (2 X 50 mL) and dried over magnesium sulfate. The product was purified by flash chromatography using 2% methanol in methylene chloride and recrystallized from methanol to give the product as a colorless solid, 0.425 g (29%): IR 1722,1671,1630, and 1501 cm'1; MS m/z 497 (MH+); XH NMR (DMSO-d6) 5 2.55-2.67 (m, 6 H), 2.90-2.98 (m, 4 H), 3.77 (s, 3 H), 3.84 (s, 3 H), 3.85 (s, 3 H), 4.03-4.07 (m, 2 H), 6.84-6.94 5). A mixture of 2a (8.0 g, 21.5 mmol) and methyl vinyl sulfone (4.08 mL, 46.6 mmol) in DMF (100 mL) was stirred at room temperature for 4 days.…”

“…Methyl 3-[2-[4-(2-Methoxyphenyl)piperazin-l-yl]ethyl]furo[3,4-tf]pyrimidine-2,4-dione-l-£rans-propenoate (5). A mixture of 2a (4.0 g, 10.8 mmol) and methyl propiolate (1.1 mL, 12 mmol) in DMF (50 mL) was stirred at room temperature 16 h. The resultant solution was worked up as described for 3a and 4a to give the product as a colorless solid, 4.8 g (97%), after recrystallization from acetonitrile/water: mp 168-170 °C; IR 1736, 1690, 1643, 1623, 1544, and 1498 cm'1; MS m/z 455 (MH+); >H NMR (CDC13) b 2.71-2.83 (m, 6 H), 3.05-3.13 (m, 4 H), 3.82 (s, 3 H), 3.86 (s, 3 H), 4.23 (t, J = 6.7 Hz, 2 H), 5.94 (d, J = 14.7 Hz, 1 H), 6.85-7.04 (m, 4 H), 7,81 (d, J = 1.5 Hz, 1 H), 8.21 (d, J = 1.5 Hz, 1 H), and (d, J = 14.7 Hz, 1 H).…”

Traceless Solid-Phase Synthesis of Ketones via Acid-Labile Enol Ethers: Application in the Synthesis of Natural Products and Derivatives

“…Not surprisingly, although only a limited number of reports have described the application of enol ethers in the synthesis of ketones, the preparation of ketones from vinyl ethers using a Grignard reagent was reported in 1955 [26]. The hydrolysis of vinyl ethers has been studied on numerous occasions [27,28,29]; however, this technique has not been applied for general preparative use. Among the few recent reports in this area, silyl enol ethers were enantioselectively converted to ketones by Cheon and coworkers [30,31].…”