Sodium Hydroxide → (R)-3-(4-Methanesulfonyl-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

HRID 1617961Notes

Reaction equation

HRID 1617961 reaction equation
N1CCC[C@H]1C(O)=O.[OH-].[Na+].Br[C:12]1[CH:17]=[CH:16][C:15]([C@H:18]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[CH2:19][C:20]([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([CH3:28])[CH:23]=2)=[O:21])=[CH:14][CH:13]=1.[CH3:36][S:37]([O-:39])=[O:38].[Na+]>CS(C)=O.[Cu]I.C(OCC)(=O)C.O>[CH3:36][S:37]([C:12]1[CH:17]=[CH:16][C:15]([C@H:18]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[CH2:19][C:20]([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([CH3:28])[CH:23]=2)=[O:21])=[CH:14][CH:13]=1)(=[O:39])=[O:38]

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 66666695(R)-3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one

Product 1

HCID 67015725(R)-3-(4-Methanesulfonyl-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-oneYield 57%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of L-proline (35 mg) in dimethyl sulfoxide (4 mL) was added at room temperature sodium hydroxide (12 mg). The reaction mixture was stirred at room temperature for 30 min. (R)-3-(4-Bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one (example 142, step 2, 150 mg), sodium methanesulfinate (311 mg) and copper(I) iodide (58 mg) were added. The reaction mixture was heated at 110° C. and stirred for 4 hours. Water and ethyl acetate were added, the phases were separated and the inorganic one was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (50% to 100% ethyl acetate in n-heptane) to yield the title compound as an yellow oil (57%), MS (ESI+): m/z=394.0 ([M+H]+).

Workup

  1. additionwere added
  2. customthe phases were separated
  3. extractionthe inorganic one was extracted with ethyl acetate (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography on silica gel (50% to 100% ethyl acetate in n-heptane)

Sources & evidence

ORD record
ord-7bcda64f10c04681ac5fd7ea80edb62a
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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