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

HRID 360013

Reaction equation

HRID 360013 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH:9]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:10]([C:20](=O)[CH:21]([CH3:23])[CH3:22])[C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])=[CH:4][CH:3]=1.[NH2:32][CH2:33][CH2:34][CH:35]([O:39][CH2:40][CH3:41])[O:36][CH2:37][CH3:38].C(O)(=O)C(C)(C)C>C1(C)C=CC=CC=1>[CH2:37]([O:36][CH:35]([O:39][CH2:40][CH3:41])[CH2:34][CH2:33][N:32]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[C:9]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:10]([C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])=[C:20]1[CH:21]([CH3:22])[CH3:23])[CH3:38]

Participants

5

Reactant 3

HCID 6417Pivalic acidHCID 5210291-Amino-3,3-diethoxypropaneHCID 99098724-(4-Fluorophenyl)-2-(2-methyl-1-oxopropyl)-4-oxo-3,N-diphenylbutanamide

Product 1

HCID 110497051-(3,3-diethoxypropyl)-5-(4-fluorophenyl)-2-(1-methyl-ethyl)-N,4-diphenyl-1H-pyrrole-3-carboxamideYield 81.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

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, 5%0 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 1o 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-lH-pyrrole-3-carboxamide; mp 125.1°-127.7° C. after recrystallization from ethanol

Workup

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

Sources & evidence

ORD record
ord-8a64b544e7f141a48d4d34f61082a2d9
Source dataset
uspto-grants-1991_03
Patent number
US05003080

Linked notes

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