3-(1,1-diMethylethyl)-7a-ethenyldihydro-, (3R,7aR)-1H,3H-Pyrrolo[1,2-c]oxazole-1,5(6H)-dione

To a 3-neck 1-L flask equipped with a thermometer and mechanical stirrer were charged PhTo a 3-neck 1-L flask equipped with a thermometer and mechanical stirrer were charged PhTo a 500 mL three-necked flask (1) equipped with an agitator, thermometer, and a nitrogen inlet were added XVI (30.0 g, 132 mmol) and THF (300 mL). After cooling mixture to -20 C., lithium tri(t-butoxy)aluminum hydride (1 M THF; 162 mL) was added over 2 h while maintaining the temperature around -20 C. Temperature was then raised to 0 C. over 12 h. The reaction is quenched with the addition of EtOAc (12.0 mL) over 30 min, followed by agitation for 30 min at 0 C., and then slow addition of glacial AcOH (12.0 mL) over 30 min. To another 1-L three-necked flask (2) equipped with an agitator, thermometer, and a nitrogen inlet were added finely ground sodium sulfate decahydrate (30 g, 93 mol) and THF (150 mL) at 0 C. The reaction mixture in flask (1) was slowly transferred to flask (2) containing the sodium sulfate decahydrate solution while maintaining the temperature at 0 C. The temperature of flask (2) was raised over a 1 h period and agitated for 1 h at 20 C. The contents of flask (2) were filtered, the wet cake was washed three times with THF (180 mL, 120 mL, and then 120 mL), and the filtrates were combined and concentrated in vacuum to 60 mL. To a 1000 mL three-necked flask (3) equipped with an agitator, thermometer, and a nitrogen inlet was added water (300 mL). The mixture from flask (2) was cooled to 5 C. and then added to the water with high agitation over a 2 h period, whereupon the product precipitated. The slurry was concentrated in vacuum to 450 mL and the solid was isolated via filtration. The wet cake was dried at 50 C. for 12 h to afford 25.1 g of the compound of formula H as a white/off white solid in 83% yield. Mp 88 C. 1H-NMR 500 MHz (DMSO-d6) delta 6.92 (d, J=3.9 Hz, 1H), 6.03 (dd, J=15.8, 11.1 Hz, 1H), 5.36 (d, J=3.9 Hz, 1H), 5.24 (d, J=17.6 Hz, 1H), 5.11 (d, J=11.1 Hz, 1H), 4.75 (s, 1H), 2.72 (ddd, J=16.8, 10.2, 8.7 Hz, 1H), 2.28 (ddd, J=16.7, 10.5, 3.7 Hz, 1H), 2.45 (ddd, J=12.8, 10.4, 8.9 Hz, 1H), 1.82 (ddd, J=12.9, 10.5, 3.7 Hz, 1H), 0.85 (s, 9H). 13C-NMR (125 MHz DMSO-d6) delta 180.7, 142.1, 113.3, 96.2, 93.9, 73.6, 34.5, 33.2, 26.8, 25.9 ppm. LC/MS calculated mass for C12H20NO3 [M+H]+(m/z) 226.14377. found 226.14398.To a 3-neck 1-L flask equipped with a thermometer and mechanical stirrer were charged Ph3PCH3Br (122.9 g; 344.1 mmol) and toluene (100 mL). At 10 C., a solution of NaHMDS in toluene (540 mL, 13%) was added slowly to maintain the temperature at 10 C. This slurry was agitated at 10 C. for 1 h and then added slowly to a slurry of XV (50 g, 222 mmol) in toluene (100 mL) at 10 C., over a period of 2-4 h via peristaltic pump. After stirring for an additional hour, the batch was quenched into a solution of NaCl (10% aqueous), AcOH (38.5 mL, 666 mmol), and toluene (50 mL) over 30 min at 25 C. The resulting mixture was stirred for 30 min and the layers were settled, split and the lower aqueous layer was removed. The organic layer was then treated with MgCl2 powder (70 g, 776 mmol) for 2 h at RT. The solids were then filtered off and the solid MgCl2-triphenylphosphin oxide complex was washed with MTBE (100 mL). The organic filtrates were combined, washed with aq. NaCl (100 mL, 10%) and concentrated to 100 mL in vacuum. To the resulting slurry was charged heptane (400 mL) and the volume was reduced to 100 mL in vacuum. Additional heptane (400 mL) was added and the volume was reduced to 250 mL in vacuum. A third portion of heptane (400 mL) was added; the batch was then cooled to 0 C. over 2 h and stirred for another 2 h at this temperature. The solids were then removed by filtration and washed with ice-cold N-heptane (200 mL). The wet cake was dried under vacuum at 30 C. for 18 h to produce 62 g of XVI (63% yield) as an off-white solid. Mp 85 C.-87 C. 1H-NMR (CDCl3) delta 5.98 (m, 1H), 5.31 (m, 3H), 2.56 (m, 1H), 2.17 (m, 3H), 0.81 (s, 9H). ES-MS: [M+H+]calcd for C12H18NO3: 224.12. found: 224.38.

Molecular Weight:223.27
XLogP3:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:223.12084340
Monoisotopic Mass:223.12084340
Topological Polar Surface Area:46.6
Heavy Atom Count:16
Complexity:369
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes