Pivalic acid → 1-(3,3-diethoxypropyl)-5-(4-fluorophenyl)-2-(1-methyl-ethyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide

関与物質

反応条件

反応手順

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-1 H-pyrrole-3-carboxamide; mp 125.1°-127.7° C. after recrystallization from ethanol.

情報源と証拠