HCID 19867638, compound → HCID 14460148, compound

HRID 1720691Notes

Reaction equation

HRID 1720691 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:17]=[C:16]([CH:26]([CH3:28])[CH3:27])[C:15]=2[C:29](OCC)=[O:30])=[CH:10][CH:9]=1>CCOCC>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:17]=[C:16]([CH:26]([CH3:28])[CH3:27])[C:15]=2[CH2:29][OH:30])=[CH:10][CH:9]=1

Participants

4

Reactant 2

HCID 19867638HCID 19867638, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 14460148HCID 14460148, compoundYield 77.8%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A slurry of LiAlH4 (775 mg, 20.4 mmol) in dry Et2O (70 ml) at 0° C. was treated with a solution of 4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinecarboxylic acid, ethyl ester (4.80 gm, 13.2 mmol) in Et2O (5 ml). After 2.5 hours, the reaction was quenched and diluted with H2O and the aqueous layer was extracted twice with Et2O and once with EtOAc. The combined organic layers were washed with H2O and brine, then dried (Na2SO4), filtered and stripped. The resulting solid was dissolved in hot EtOAc and directly chromatographed (flash, Merck SiO2, 20% EtOAc in hexane) to give crude 4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinemethanol. Recrystallization from hot hexane/EtOAc gave 4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinemethanol (3.30 gm) as a white solid. The mother liquor was stripped and recrystallized again to give an additional 230 mg of product (total 3.53 gm, 84%).

Workup

  1. customthe reaction was quenched
  2. additiondiluted with H2O
  3. extractionthe aqueous layer was extracted twice with Et2O and once with EtOAc
  4. washThe combined organic layers were washed with H2O and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. dissolutionThe resulting solid was dissolved in hot EtOAc
  8. customdirectly chromatographed (flash, Merck SiO2, 20% EtOAc in hexane)
  9. customto give crude 4-(4-fluorophenyl)-2-(1-methylethyl)-6-phenyl-3-pyridinemethanol
  10. customRecrystallization from hot hexane/EtOAc

Sources & evidence

ORD record
ord-5bb437d851c044d0b9e8c47491fb8d00
Source dataset
uspto-grants-1996_04
Patent number
US05506219

Reaction notes

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