Diisopropylamine → (r)-5-[2-(4-Fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (s)-2-hydroxy-1,2,2-triphenylethyl ester

HRID 1159497

Reaktionsgleichung

Reaktionsgleichung von HRID 1159497
[CH3:1][C:2]([O:4][C@H:5]([C:12]([OH:25])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[Li+].CC([N-]C(C)C)C.C(NC(C)C)(C)C.[F:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[N:52]([CH2:53][CH2:54][CH:55]=[O:56])[C:51]([CH:57]([CH3:59])[CH3:58])=[C:50]([C:60]([NH:62][C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)=[O:61])[C:49]=2[C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)=[CH:44][CH:43]=1>C1COCC1.O.CC(O)=O>[F:41][C:42]1[CH:43]=[CH:44][C:45]([C:48]2[N:52]([CH2:53][CH2:54][C@@H:55]([OH:56])[CH2:1][C:2]([O:4][C@@H:5]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:12]([OH:25])([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:3])[C:51]([CH:57]([CH3:59])[CH3:58])=[C:50]([C:60]([NH:62][C:63]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)=[O:61])[C:49]=2[C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)=[CH:46][CH:47]=1

Komponenten

8

Edukt 4

HCID 7912DiisopropylamineHCID 7360481,2-Ethanediol, 1,1,2-triphenyl-, 2-acetate, (2S)-HCID 2724682Lithium diisopropylamideHCID 113055725-(4-Fluorophenyl)-2-(1-methylethyl)-1-(3-oxopropyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide

Produkt 1

HCID 11193615(r)-5-[2-(4-Fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1h-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (s)-2-hydroxy-1,2,2-triphenylethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a suspension of S-(−)-2-Hydroxy-1,2,2-triphenylethyl acetate (40.2 g) in 300 mL anhydrous THF at −10 to 0° C. was added a solution of LDA prepared by reaction of diisopropylamine (46.5 mL) with 2.5 M n-BuLi/hexanes (97 mL) in 300 mL anhydrous THF at −5 to 0° C. After stirring at 0° C. for 30 min the mixture was cooled to −78° C. Then, a solution of 5-(4-fluorophenyl)-2-(1-methylethyl)-1-(3-oxopropyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide 1 (50 g) in 280 mL anhydrous THF was added dropwise and maintained at −78° C. for 30 min. After adding 25 mL AcOH and 250 mL water the mixture was allowed to warm to room temperature. The layers were separated and the organic layer was washed and dried. After evaporation of the solvent the crude product was obtained (94 g). Analytical data are consistent with that from the prior art.

Aufarbeitung

  1. temperaturewas cooled to −78° C
  2. temperaturemaintained at −78° C. for 30 min
  3. temperatureto warm to room temperature
  4. customThe layers were separated
  5. washthe organic layer was washed
  6. customdried
  7. customAfter evaporation of the solvent the crude product
  8. customwas obtained (94 g)

Quellen und Nachweise

ORD-Eintrag
ord-59897b74b76b4132a0e90e1a17c69d0b
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07812179B2

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