反应详情

To a nitrogen purged flask equipped with a mechanical stirrer is added 130 kg (311 mol) of (±)4-fluoro-α-[2-methyl-1-oxopropyl]-γ-oxo-N,β-diphenylbenzenebutaneamide mixture of [R-(R*,R*)], [R-(R*,S*)], [S-(R*,R*)] and [S-(R*,S*)] isomers, 540 L of heptanes and 60 L of toluene, 59 kg (400 mol) of 3-amino-1,1-diethoxypropane, and 22.3 kg (218 mol) of pivalic acid. The mixture is stirred and heated to reflux, removing water with a Dean Stark trap. The mixture is refluxed 32 hours and slowly cooled to 60°-65° C., diluted with 500 L of 2-propanol-water (3:2), seeded, and cooled to 20°-25° C. The product is isolated by filtration, washed with 300 L of 2-propanol, and dried in vacuo to yield 133.5 kg of 1-(3,3-diethoxypropyl)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide; mp 125.1°-127.7° C. after recrystallization from ethanol.

1. customTo a nitrogen purged flask equipped with a mechanical stirrer
2. additionis added
3. temperatureheated
4. temperatureto reflux
5. customremoving water with a Dean Stark trap
6. temperatureThe mixture is refluxed 32 hours
7. temperatureslowly cooled to 60°-65° C.
8. additiondiluted with 500 L of 2-propanol-water (3:2)
9. temperaturecooled to 20°-25° C
10. customThe product is isolated by filtration
11. washwashed with 300 L of 2-propanol
12. customdried in vacuo