Methanol → 1,1-dimethyleth-1-yl (3R,5S,E)-7-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3,5-dihydroxy-6-heptenoate

HRID 2050586

Reaktionsgleichung

Reaktionsgleichung von HRID 2050586
CO.C(B(CC)CC)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:18]=[C:19]([CH:44]([CH3:46])[CH3:45])[N:20](/[CH:29]=[CH:30]/[C@@H:31]([OH:43])[CH2:32][C:33](=[O:42])[CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[CH:13][CH:12]=1.[BH4-].[Na+]>C1COCC1>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:18]=[C:19]([CH:44]([CH3:46])[CH3:45])[N:20](/[CH:29]=[CH:30]/[C@@H:31]([OH:43])[CH2:32][C@@H:33]([OH:42])[CH2:34][C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])[C:21]=2[C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)=[CH:13][CH:12]=1

Komponenten

6

Edukt 4

HCID 887MethanolHCID 7357TriethylboraneHCID 4311764Sodium borohydrideHCID 148498021,1-Dimethyleth-1-yl (5S,E)-7-[4,5-bis-(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-5-hydroxy-3-oxo-6-heptenoate

Produkt 1

HCID 148498511,1-dimethyleth-1-yl (3R,5S,E)-7-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3,5-dihydroxy-6-heptenoateAusbeute 99,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of dry THF (16 ml) and dry methanol (4 ml) under nitrogen at room temperature was treated with a solution of triethyl borane (1.0M in THF, 2.32 ml). After 1 h the mixture was cooled to -78° and treated with a solution of 1,1-dimethyleth-1-yl (5S,E)-7-[4,5-bis-(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-5-hydroxy-3-oxo-6-heptenoate (1.075 g) in THF (4:1) (15 ml) plus washings (5 ml). After a further 1 h at -75° the mixture was treated with sodium borohydride (88 mg). After 21/2 h the mixture was quenched with saturated aqueous ammonium chloride solution (2 ml) and allowed to warm. The mixture was then diluted with water (100 ml) and extracted with ethyl acetate (3×70 ml). The combined extracts were dried and evaporated and the residue was azeotroped with methanol (3×30 ml). This gave a pale yellow solid (1.076 g) which was crystallised from ether-cyclohexane to give the title compound (739 mg) as white fluffy crystals, δ(CDCl3) 1.3-1.65 (m, 2H, CH(OH)CH2CH(OH)), 1.40 (d, J 7 Hz, 6H, --CH(CH3)2), 1.46 (s, 9H, --C(CH3)3), 2.35 (d, J 7 Hz, 2H, CH2CO2R), 3.15 (septet, J 7 Hz, 1H, --CH(CH3)2), 3.77, 3.81 (2s, 2H, CH(OH)CH2CH(OH), 4.12 (m, 1H, CH(OH)CH2CO2), 4.42 (m, 1H, =CHCH(OH)CH2 --), 5.30 (dd, J 14 and 7 Hz, 1H, N--CH=CH--), 6.67 (d, J 14 Hz, 1H, N--CH=CH--), 6.90 and 7.09 (2t, J 9 Hz each 2H, C-3 and C-5 protons of 4-fluorophenyls), 7.2-7.43 (m, 4H, C-2 and C-6 protons of 4-fluorophenyls).

Aufarbeitung

  1. temperatureAfter 1 h the mixture was cooled to -78°
  2. customAfter 21/2 h the mixture was quenched with saturated aqueous ammonium chloride solution (2 ml)
  3. temperatureto warm
  4. additionThe mixture was then diluted with water (100 ml)
  5. extractionextracted with ethyl acetate (3×70 ml)
  6. customThe combined extracts were dried
  7. customevaporated
  8. customthe residue was azeotroped with methanol (3×30 ml)

Quellen und Nachweise

ORD-Eintrag
ord-6ef4b6e2439f445bb749379eff67d115
Quelldatensatz
uspto-grants-1991_05
Patentnummer
US05013749

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