Hydrochloric Acid → 2-(3-Formyl-benzyl)-1,1-dioxo-1lambda6 isothiazolidine-3-carboxylic acid methyl ester

HRID 1879463Notes

Reaction equation

HRID 1879463 reaction equation
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[O:7].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:17][O:18][C:19]([CH:21]1[CH2:25][CH2:24][S:23](=[O:27])(=[O:26])[NH:22]1)=[O:20].[CH2:28]([O:30][C:31]([CH:33]1[CH2:37][CH2:36][S:35](=[O:39])(=[O:38])[NH:34]1)=[O:32])[CH3:29].[Cl-].[NH4+].Cl>CN(C)C=O.ClCCl>[CH2:28]([O:30][C:31]([CH:33]1[CH2:37][CH2:36][S:35](=[O:38])(=[O:39])[N:34]1[CH2:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:5]([CH:6]=[O:7])[CH:4]=1)=[O:32])[CH3:29].[CH3:17][O:18][C:19]([CH:21]1[CH2:25][CH2:24][S:23](=[O:27])(=[O:26])[N:22]1[CH2:2][C:3]1[CH:10]=[CH:9][CH:8]=[C:5]([CH:6]=[O:7])[CH:4]=1)=[O:20]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 71278253-(Bromomethyl)benzaldehydeHCID 11240805Methyl 1,1-dioxo-1lambda6,2-thiazolidine-3-carboxylateHCID 53487526Ethyl 1,1-dioxo-isothiazolidine-3-carboxylate2×

Product 2

HCID 582804492-(3-Formyl-benzyl)-1,1-dioxo-1lambda6 isothiazolidine-3-carboxylic acid ethyl esterYield 37%HCID 866538012-(3-Formyl-benzyl)-1,1-dioxo-1lambda6 isothiazolidine-3-carboxylic acid methyl esterYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

3-Bromomethyl-benzaldehyde (2.44 g, 12.3 mmol) and cesium carbonate (9.08 g, 27.9 mmol) were added to a solution of a 4:3 mixture of 1,1-dioxo-isothiazolidine-3-carboxylic acid methyl ester and 1,1-dioxo-isothiazolidine-3-carboxylic acid ethyl ester (Intermediate 7 Step 2; 2.01 g, 10.8 mmol) in N,N-dimethylformamide (60 mL). The mixture was stirred at room temperature for 20 h and then dichloromethane (100 mL) was added. Saturated aqueous ammonium chloride solution (25 mL) was added followed by 1 M hydrochloric acid to bring the pH to 2-3. The two layers were separated and the organic layer was washed twice with brine. The solution was dried over sodium sulfate, and filtered. Celite was added and the solvents were evaporated under reduced pressure. The residue (containing the mixture of crude products coated onto Celite) was purified using flash chromatography (Analogix SF40-240 g Si), eluting with 30-70% ethyl acetate/hexanes to give 2-(3-formyl-benzyl)-1,1-dioxo-1λ6 isothiazolidine-3-carboxylic acid ethyl ester (first eluting peak; 1.26 g, 37%) and 2-(3-formyl-benzyl)-1,1-dioxo-1λ6 isothiazolidine-3-carboxylic acid methyl ester (second eluting peak; 1.69 g, 53%).

Workup

  1. customThe two layers were separated
  2. washthe organic layer was washed twice with brine
  3. dry with materialThe solution was dried over sodium sulfate
  4. filtrationfiltered
  5. additionCelite was added
  6. customthe solvents were evaporated under reduced pressure
  7. additionThe residue (containing
  8. additionthe mixture of crude products coated onto Celite)
  9. customwas purified
  10. washeluting with 30-70% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-1f0561d9bc064e5e8cdbcc9b86bca687
Source dataset
uspto-grants-2012_11
Patent number
US08314250B2

Reaction notes

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