2,4,6-Trimethylpyridine → 1-Cyclohexyl-2-(4,6-dimethylpyridin-2-ylmethyl)-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-ol

HRID 1510896Notes

Reaction equation

HRID 1510896 reaction equation
[N:1]1[C:6]([CH3:7])=[CH:5][C:4]([CH3:8])=[CH:3][C:2]=1[CH3:9].C([Li])(C)(C)C.[CH:15]1([CH2:21][C:22](=[O:36])[CH2:23][C:24]([C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=2[O:34][CH3:35])([CH3:26])[CH3:25])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>C1COCC1>[CH:15]1([CH2:21][C:22]([CH2:9][C:2]2[CH:3]=[C:4]([CH3:8])[CH:5]=[C:6]([CH3:7])[N:1]=2)([OH:36])[CH2:23][C:24]([C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=2[O:34][CH3:35])([CH3:26])[CH3:25])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 79532,4,6-TrimethylpyridineHCID 223986261-Cyclohexyl-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-oneHCID 178418306HCID 178418306, compound

Product 1

HCID 223986011-Cyclohexyl-2-(4,6-dimethylpyridin-2-ylmethyl)-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-olYield 55.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of collidine (0.113 g) in THF (1 mL) cooled to −70° C. was added dropwise over 3 minutes tert-butyl lithium (1.7 M in pentane, 0.55 mL). The mixture was stirred for 5 minutes and then 1-cyclohexyl-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (Example 15) (0.095 g) in THF (0.5 mL) was added dropwise. After 10 minutes at −70° C., the reaction was quenched by addition of EtOH (0.2 mL) and warmed to room temperature. The mixture was diluted with EtOAc, washed with water, dried over sodium sulfate, filtered, and evaporated. The residue was fractionated by preparative layer chromatography (developer: methylene chloride-EtOAc (99:1)) followed by preparative layer chromatography (developer:hexanes-methylene chloride-EtOH (1:1:0.01)) to give the title compound as an oil (73 mg).

Workup

  1. waitAfter 10 minutes at −70° C.
  2. customthe reaction was quenched by addition of EtOH (0.2 mL)
  3. additionThe mixture was diluted with EtOAc
  4. washwashed with water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-5491e537bac04f97a7317ef23aa55614
Source dataset
uspto-grants-2012_07
Patent number
US08212040B2

Reaction notes

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