Hydrochloric Acid → HCID 86749412, compound

HRID 1720707Notes

Reaction equation

HRID 1720707 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].[Li]CCCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28](/[CH:29]=[CH:30]/[CH:31]=[O:32])=[C:27]([CH:33]([CH3:35])[CH3:34])[CH:26]=[C:25]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:24]=2)=[CH:19][CH:18]=1.Cl.C([O-])(O)=O.[Na+]>C1COCC1.CCOCC.O>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28](/[CH:29]=[CH:30]/[CH:31]([OH:32])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])=[C:27]([CH:33]([CH3:35])[CH3:34])[CH:26]=[C:25]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[N:24]=2)=[CH:19][CH:18]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 21471477HCID 21471477, compoundHCID 178418339Butyllithium

Product 1

HCID 86749412HCID 86749412, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Methyl acetoacetate (160 mg, 1.38 mmol) was dropwise to a slurry of NaH (60% in mineral oil, 55.1 mg, 1.38 mmol) in dry THF (3.5 ml) at 0° C. After 15 minutes, n-BuLi (1.5M in hexane, 830 ul, 1.25 mmol) was added and the mixture was stirred an additional 15 minutes. The bright yellow solution was cooled to -78° C. and treated with a solution of (E)-3-[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]-2-propenal (317 mg, 0.92 mmol) in THF (2 ml). Stirring continued for 20 minutes, after which time the reaction was warmed to 0° C. and stirred for an additional 20 minutes. The yellow-orange solution was then added to a biphasic mixture of 1N HCl (3 ml), H2O (15 ml), and Et2O (30 ml). The aqueous layer was made slightly basic with saturated NaHCO3 and the phases were separated. The aqueous layer was diluted with saturated NH4Cl and was extracted with Et2O once again. The combined organic layers were washed with brine and dried (Na2SO4). Filtration and removal of the solvent afforded an oil which was chromatographed (flash, Merck SiO2, 35% EtOAc in hexane) to give (E)-7-[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]-5-hydroxy-3-oxo-6-heptenoic acid, methyl ester as an oily solid (187 mg, 44%).

Workup

  1. stirringStirring
  2. waitcontinued for 20 minutes
  3. temperatureafter which time the reaction was warmed to 0° C.
  4. stirringstirred for an additional 20 minutes
  5. customthe phases were separated
  6. additionThe aqueous layer was diluted with saturated NH4Cl
  7. extractionwas extracted with Et2O once again
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationFiltration and removal of the solvent
  11. customafforded an oil which
  12. customwas chromatographed (flash, Merck SiO2, 35% EtOAc in hexane)

Sources & evidence

ORD record
ord-8e93e9216fa343b1b75a2835ba5f30e3
Source dataset
uspto-grants-1996_04
Patent number
US05506219

Reaction notes

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