Réaction #7316

ord-28f25661c0c749d289fe2eb55676d218

Équation de réaction

CC(C)c1c(C(=O)Nc2ccccc2)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H](O)C[C@@H](O)CC(=O)OC(C)(C)C
(3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoyl-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid, t-butyl ester
CO.O.[K+].[OH-]
KOH MeOH Water
CC(C)O
IPA
Cl
HCl
→
CC(C)c1c(C(=O)Nc2ccccc2)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H](O)C[C@@H](O)CC(=O)O
(3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoyl-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid

Réactifs

CC(C)c1c(C(=O)Nc2ccccc2)c(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H](O)C[C@@H](O)CC(=O)OC(C)(C)C
(3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoyl-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid, t-butyl ester
CO.O.[K+].[OH-]
KOH MeOH Water
CC(C)O
IPA
Cl
HCl

Réactifs

Aucun

Solvants

—
Hexanes
Cc1ccccc1
toluene

Conditions de réaction

Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    AutretR(3R,5R)=26.97 min.
  2. 2
    AutretR(3S,5S)=33.8 min.
  3. 3
    AutretR(3R,5S)=38.1 min.
  4. 4
    AutretR(3S,5R)=61.0 min.

Mode opératoire

The crude (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoyl-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid, t-butyl ester (VI-A) was converted to the acid using an excess of KOH/MeOH/Water, followed by lactonization in toluene with catalytic HCl. Chiral HPLC analysis (ChiralCel OF; 1 ml/min; 60° C.; 254 nm; 20% IPA:Hexanes) tR(3R,5R)=26.97 min./tR(3S,5S)=33.8 min. tR(3R,5S)=38.1 min./tR(3S,5R)=61.0 min.) indicated an enantiomeric excess of the syn isomer of 85%, favoring the (R,R) configuration.

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US07084282B2uspto-grants-2006_08