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

Reaction equation

HRID 892961 reaction equation
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

Participants

8

Reactant 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

Product 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-pentenoateYield 94.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-a2a706e1f63f40f1bceb43c3e3934459
Source dataset
uspto-grants-1992_06
Patent number
US05120848

Linked notes

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