HCID 19867638, compound → HCID 14460148, compound

HRID 2295183Notes

Reaction equation

HRID 2295183 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 (Na2 SO4), 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. customdried (Na2 SO4)
  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-023983f0e7c04563871c3ae8a01355fd
Source dataset
uspto-grants-1997_11
Patent number
US05691322

Reaction notes

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