Hydrochloric Acid → HCID 86749405, compound

HRID 2295186Notes

Reaction equation

HRID 2295186 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[CH:28]=[C:27]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:26]=[C:25]([CH:35]([CH3:37])[CH3:36])[C:24]=2/[CH:38]=[CH:39]/[CH:40]=[O:41])=[CH:19][CH:18]=1.Cl.C([O-])(O)=O.[Na+]>C1COCC1.O.CCOCC>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[C:27]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:26]=[C:25]([CH:35]([CH3:37])[CH3:36])[C:24]=2/[CH:38]=[CH:39]/[CH:40]([OH:41])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])=[CH:19][CH:18]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 15107982HCID 15107982, compoundHCID 178418339Butyllithium

Product 1

HCID 86749405HCID 86749405, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Methyl acetoacetate (272 mg, 2.34 mmol) was added dropwise to a slurry of NaH (60% in mineral oil, 93.7 mg, 23.4 mmol) in dry THF (5.5 ml) at 0° C. After 15 minutes, the solution was treated with n-BuLi (1.6M in hexanes, 1.11 ml, 1.78 mmol) and stirred an additional 15 minutes. (E)-3-[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinyl]-2-propenal (560 mg, 1.62 mmol) in THF (3.0 ml) was added, resulting in an orange solution. After 25 minutes, the solution was poured into a biphasic mixture Et2O (30 ml), 1N HCl (4.5 ml) and H2O (16 ml). The aqueous phase was neutralized with saturated NaHCO3 and the layers were separated. The aqueous layer was extracted again with Et2O and the combined Et2O layers were washed with brine and dried (Na2 SO4). Filtration and solvent removal afforded an oil which was chromatographed (Flash, Merck SiO2, 30% EtOAc in hexane) to give (E)-7-[4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinyl]-5-hydroxy-3-oxo-6-heptenoic acid, methyl ester (387 mg, 52%) as a light yellow oil.

Workup

  1. customresulting in an orange solution
  2. waitAfter 25 minutes
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted again with Et2O
  5. washthe combined Et2O layers were washed with brine
  6. customdried (Na2 SO4)
  7. filtrationFiltration and solvent removal
  8. customafforded an oil which
  9. customwas chromatographed (Flash, Merck SiO2, 30% EtOAc in hexane)

Sources & evidence

ORD record
ord-a7fb02f6ddb14cb8a6990284e401d07b
Source dataset
uspto-grants-1997_11
Patent number
US05691322

Reaction notes

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