Hydrochloric Acid → methyl (R)-4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-ylmethyl)benzoate

HRID 2411168Notes

Reaction equation

HRID 2411168 reaction equation
[CH3:1][C@@H:2]1[CH2:6][CH2:5][S:4](=[O:8])(=[O:7])[NH:3]1.[H-].[Na+].Br[CH2:12][C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1.Cl>O1CCCC1.CN(C)C=O>[CH3:1][C@@H:2]1[CH2:6][CH2:5][S:4](=[O:8])(=[O:7])[N:3]1[CH2:12][C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 16664802(R)-3-methylisothiazolidine 1,1-dioxide

Product 1

HCID 71261169methyl (R)-4-(3-methyl-1,1-dioxo-1lambda6-isothiazolidin-2-ylmethyl)benzoateYield 56.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Under a nitrogen stream, (R)-3-methylisothiazolidine 1,1-dioxide (149 mg) described in Preparation Example 2 was dissolved in a solution of tetrahydrofuran (5 mL) and N,N-dimethylformamide (4 mL), sodium hydride (44 mg) was added under ice-cooling, and the mixture was stirred at the same temperature for 15 min. Then, a solution of methyl 4-bromomethylbenzoate (229 mg) in tetrahydrofuran (5 mL) was added, and the mixture was stirred under ice-cooling for 1.5 hr, and at room temperature for 2 hr. To the reaction mixture was added 0.5N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (159 mg).

Workup

  1. additionwas added under ice-
  2. temperaturecooling
  3. stirringthe mixture was stirred under ice-
  4. temperaturecooling for 1.5 hr
  5. waitat room temperature for 2 hr
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with water and saturated brine
  8. customthe solvent was evaporated
  9. customThe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-c9406b666cfc4c72a9d32b022a4f9fd4
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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