Sodium Hydroxide → (R)-1-Methyl-5-(3-(4-(methylsulfonyl)phenyl)-3-o-tolylpropanoyl)pyridin-2(1H)-one

HRID 1618045Notes

Reaction equation

HRID 1618045 reaction equation
N1CCC[C@H]1C(O)=O.[OH-].[Na+].Br[C:12]1[CH:17]=[CH:16][C:15]([C@H:18]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:36])[CH2:19][C:20]([C:22]2[CH:23]=[CH:24][C:25](=[O:29])[N:26]([CH3:28])[CH:27]=2)=[O:21])=[CH:14][CH:13]=1.[CH3:37][S:38]([O-:40])=[O:39].[Na+]>[Cu]I.CS(C)=O>[CH3:28][N:26]1[CH:27]=[C:22]([C:20](=[O:21])[CH2:19][C@H:18]([C:15]2[CH:14]=[CH:13][C:12]([S:38]([CH3:37])(=[O:40])=[O:39])=[CH:17][CH:16]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:36])[CH:23]=[CH:24][C:25]1=[O:29]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 66668696(R)-5-(3-(4-Bromophenyl)-3-o-tolylpropanoyl)-1-methylpyridin-2(1H)-one

Product 1

HCID 66668634(R)-1-Methyl-5-(3-(4-(methylsulfonyl)phenyl)-3-o-tolylpropanoyl)pyridin-2(1H)-oneYield 88.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

L-proline (44.9 mg, 390 μmol) was combined with dimethyl sulfoxide (5 mL), then sodium hydroxide (15.6 mg, 390 μmol) was added and the reaction stirred at room temperature for 30 min. Then (R)-5-(3-(4-bromophenyl)-3-o-tolylpropanoyl)-1-methylpyridin-2(1H)-one (example 223, step 3; 200 mg, 487 μmol), sodium methanesulfinate (410 mg, 3.9 mmol) and copper(I) iodide (74.3 mg, 390 μmol) were added. The reaction mixture was heated at 120° C. for 21 h, then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated. Chromatography (SiO2; gradient ethyl acetate/heptane 1:1 to ethyl acetate) afforded the title compound (176 mg, 88%). White foam, MS (ESI+): m/z=: 410.2 [M+H]+.

Workup

  1. temperatureThe reaction mixture was heated at 120° C. for 21 h
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-73a5b1577ebe4f178d4be343c2bb6f1c
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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