Methane → 5-Hydroxy-3,3-dimethyl-2,3-dihydro-1lambda6,2-benzothiazole-1,1-dione

HRID 2083917Notes

Reaction equation

HRID 2083917 reaction equation
C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[S:10](=[O:12])(=[O:11])[NH:9][C:8](=O)[C:7]=2[CH:14]=1.[CH4:15].O=S(Cl)Cl.[CH3:20][Mg]Cl>CN(C=O)C.C1COCC1>[CH3:15][C:8]1([CH3:20])[C:7]2[CH:14]=[C:3]([OH:2])[CH:4]=[CH:5][C:6]=2[S:10](=[O:12])(=[O:11])[NH:9]1

Participants

7

Reactant 4

HCID 297MethaneHCID 24386Thionyl ChlorideHCID 123814981,2-Benzisothiazol-3(2H)-one, 5-methoxy-, 1,1-dioxideHCID 178418332HCID 178418332, compound

Product 1

HCID 129922855-Hydroxy-3,3-dimethyl-2,3-dihydro-1lambda6,2-benzothiazole-1,1-dioneYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

Saccharine 5a (290 mg, 4.08 mmol) was dissolved in xylenes (10 mL) containing a small amount of activated charcoal (50 mg). DMF (2 drops) and freshly distilled SOCl2 (0.30 mL, 4.08 mmol) were added and the resulting mixture was heated to reflux for 15 hours. The solution was then cooled to room temperature and concentrated in vacuo to give a paste. The paste was dissolved in THF and the resulting solution was then added dropwise to a solution of MeMgCl (1.36 mL of a 3.0 M solution in THF, 4.08 mmol) in THF (7 mL). The resulting solution was stirred at 40° C. for 24 hours. After removal of solvent, the desired compound (124 mg, 40%) was obtained by flash chromatography (40 to 60% EtOAc in hexanes). To a solution of this material (100 mg, 0.44 mmol) in CH2Cl2 (50 mL) at −78° C. was added a 1.0 M solution of BBr3 (2.64 mL, 2.64 mmol) in CH2Cl2. The resulting mixture was stirred for 16 hours at ambient temperature. Careful quenching by the addition of H2O was followed by extraction with EtOAc. The combined organic extracts were washed with water and brine then dried over MgSO4. Compound 6a (54 mg, 58%) was delivered by flash chromatography (40 to 60% EtOAc in hexanes).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 15 hours
  3. concentrationconcentrated in vacuo
  4. customto give a paste
  5. customAfter removal of solvent

Sources & evidence

ORD record
ord-f20a2a1e12de4eb4b09464169cd1e83d
Source dataset
uspto-grants-2004_04
Patent number
US06716836B2

Reaction notes

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