4-Methylpyridine → (R)-4-(4-bromophenyl)-1-(pyridin-4-yl)-4-o-tolylbutan-2-one

HRID 1617788Notes

Reaction equation

HRID 1617788 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH3:29])[CH2:16][C:17](N(OC)C)=[O:18])=[CH:11][CH:10]=1.C([O-])(O)=O.[Na+]>C1COCC1>[Br:8][C:9]1[CH:10]=[CH:11][C:12]([C@H:15]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH3:29])[CH2:16][C:17](=[O:18])[CH2:1][C:2]2[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=2)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 79634-MethylpyridineHCID 516892Sodium BicarbonateHCID 71813344(R)-3-(4-Bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamide

Product 1

HCID 66666163(R)-4-(4-bromophenyl)-1-(pyridin-4-yl)-4-o-tolylbutan-2-oneYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

At −78° C., to a solution of 4-methylpyridine (308 mg) in THF (7 mL) n-butyllithium (1.6M in hexane, 2.07 ml) was added. The reaction mixture was warmed slowly to rt, stirred for 1 h at that temperature, and cooled down again to −78° C. (R)-3-(4-Bromophenyl)-N-methoxy-N-methyl-3-o-tolylpropanamide (example 142, step 1; 400 mg) in THF (3 mL) was added slowly and the reaction mixture was warmed to rt and stirred for 3 h. The mixture was poured into a saturated aqueous solution of NaHCO3 (10 mL), the phases were separated, and the inorganic one was extracted with EtOAc (2×10 mL). The organic layers were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography on silica gel (30% to 60% EtOAc in n-heptane to CH2Cl2/MeOH 9:1) to yield the title compound as a yellow oil (220 mg, 51%), MS (ESI+): m/z=394.0 ([M+H]+, 1Br).

Workup

  1. additionwas added slowly
  2. temperaturethe reaction mixture was warmed to rt
  3. stirringstirred for 3 h
  4. customthe phases were separated
  5. extractionthe inorganic one was extracted with EtOAc (2×10 mL)
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash chromatography on silica gel (30% to 60% EtOAc in n-heptane to CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record
ord-f5b066beee764413a80640277c99760d
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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