Dicyclohexylamine → (S)-1-hydroxy-1,1,2-triphenyleth-2-yl (3S,E)-5-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3-hydroxy-4-pentenoate

HRID 892961

Reaktionsgleichung

Reaktionsgleichung von HRID 892961
C1(NC2CCCCC2)CCCCC1.C([Li])CCC.[C:19]([O:22][C@@H:23]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[C:24]([OH:37])([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)(=[O:21])[CH3:20].[F:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]2[N:52]=[C:53]([CH:67]([CH3:69])[CH3:68])[N:54](/[CH:63]=[CH:64]/[CH:65]=[O:66])[C:55]=2[C:56]2[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=2)=[CH:47][CH:46]=1.[Cl-].[NH4+]>C1COCC1.O>[F:44][C:45]1[CH:46]=[CH:47][C:48]([C:51]2[N:52]=[C:53]([CH:67]([CH3:69])[CH3:68])[N:54](/[CH:63]=[CH:64]/[C@@H:65]([OH:66])[CH2:20][C:19]([O:22][C@@H:23]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:24]([OH:37])([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:21])[C:55]=2[C:56]2[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=2)=[CH:49][CH:50]=1

Komponenten

8

Edukt 5

HCID 7582DicyclohexylamineHCID 25517Ammonium ChlorideHCID 7360481,2-Ethanediol, 1,1,2-triphenyl-, 2-acetate, (2S)-HCID 14849786(E)-3-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-2-propenalHCID 178418339Butyllithium

Produkt 1

HCID 14849798(S)-1-hydroxy-1,1,2-triphenyleth-2-yl (3S,E)-5-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3-hydroxy-4-pentenoateAusbeute 94,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

A solution of dry dicyclohexylamine (2.49 ml) in dry THF (30 ml) under nitrogen at 3° was treated dropwise with a solution of n-butyl lithium (1.55M in hexanes, 8.06 ml). After 25 min the solution was cannulated dropwise into a stirred suspension of (S)-1-hydroxy-1,1,2-triphenyleth-2-yl acetate (1.828 g) in dry THF (60 ml) under nitrogen at -40°, plus washings (10 ml). When the addition was complete the mixture was allowed to warm to 3°. After 20 min the solution was cooled to -40° and treated with a solution of (E)-3-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-2-propenal (1.762 g) in dry THF (35 ml) and washings (5 ml) at 3° dropwise. After 4 h the reaction mixture was treated with saturated aqueous ammonium chloride solution (20 ml) and allowed to warm. Water (200 ml) was then added and the mixture extracted with ethyl acetate (3×100 ml). The combined extracts were dried and evaporated and purified by FCC eluting with System A (7:3) to give the title compound (3.234 g) as a light brown foam, νmax (CHBr3) 2971 (OH), 1729 cm-1 (C=O) (SS:SR=93:7 as determined by pmr).

Aufarbeitung

  1. additionWhen the addition
  2. temperatureto warm to 3°
  3. temperatureAfter 20 min the solution was cooled to -40°
  4. temperatureto warm
  5. extractionthe mixture extracted with ethyl acetate (3×100 ml)
  6. customThe combined extracts were dried
  7. customevaporated
  8. custompurified by FCC
  9. washeluting with System A (7:3)

Quellen und Nachweise

ORD-Eintrag
ord-a2a706e1f63f40f1bceb43c3e3934459
Quelldatensatz
uspto-grants-1992_06
Patentnummer
US05120848

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