N,N'-Dimethylethylenediamine → ethyl (R)-2-methanesulfonyl-4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-yl)benzoate

HRID 2411153Notes

Reaction equation

HRID 2411153 reaction equation
I[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([S:13]([CH3:16])(=[O:15])=[O:14])[CH:3]=1.[CH3:17][C@@H:18]1[CH2:22][CH2:21][S:20](=[O:24])(=[O:23])[NH:19]1.CNCCNC.C(=O)([O-])[O-].[K+].[K+]>[Cu]I.O.C1(C)C=CC=CC=1>[CH3:16][S:13]([C:4]1[CH:3]=[C:2]([N:19]2[C@H:18]([CH3:17])[CH2:22][CH2:21][S:20]2(=[O:24])=[O:23])[CH:12]=[CH:11][C:5]=1[C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:15])=[O:14]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 16664802(R)-3-methylisothiazolidine 1,1-dioxideHCID 71252507Ethyl 4-iodo-2-methanesulfonylbenzoate

Product 1

HCID 71261164ethyl (R)-2-methanesulfonyl-4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-yl)benzoateYield 51.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a mixture of ethyl 4-bromo-2-methanesulfonylbenzoate (13.88 g), sodium iodide (13.54 g) and copper(I) iodide (4.30% g) were added toluene (46 mL) and N,N′-dimethylethylenediamine (4.86 mL), and the mixture was stirred with heating under reflux for 8 hr under a nitrogen stream. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The solvent was evaporated from the organic layer, the obtained residue was purified by column chromatography (hexane:ethyl acetate) to give ethyl 4-iodo-2-methanesulfonylbenzoate (10.32 g). To a mixture of the obtained ethyl 4-iodo-2-methanesulfonylbenzoate (3.22 g), (R)-3-methylisothiazolidine 1,1-dioxide (1.23 g) described in Preparation Example 2, copper(I) iodide (4.30 g), N,N′-dimethylethylenediamine (0.92 mL) and potassium carbonate (2.52 g) was added toluene (9.2 mL), and the mixture was stirred with heating under reflux for 8 hr under a nitrogen stream. The reaction mixture was cooled, water was added, and the mixture was extracted with ethyl acetate. The solvent was evaporated from the organic layer, and the obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (1.7 g).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 8 hr under a nitrogen stream
  3. temperatureThe reaction mixture was cooled
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe solvent was evaporated from the organic layer
  6. customthe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-26f015bf36e54cc5a55aa8c6cf042da9
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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