Hydrochloric Acid → HCID 46234358, compound

HRID 1920712Notes

Reaction equation

HRID 1920712 reaction equation
[C:1]([C:3]1[C:8]([F:9])=[CH:7][CH:6]=[CH:5][C:4]=1[OH:10])#[N:2].Cl[S:12]([N:15]=C=O)(=[O:14])=[O:13].C1(O)C=CC=CC=1.Cl>C1(C)C=CC=CC=1>[NH2:2][C:1]1[C:3]2[C:8]([F:9])=[CH:7][CH:6]=[CH:5][C:4]=2[O:10][S:12](=[O:14])(=[O:13])[N:15]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 996PhenolHCID 70918Chlorosulfonyl isocyanateHCID 27832162-Fluoro-6-hydroxybenzonitrile

Product 1

HCID 46234358HCID 46234358, compoundYield 6.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

8.0 g (58.3 mmol) of 2-cyano-3-fluorophenol are dissolved in 100 ml of anhydrous toluene. With exclusion of moisture and under protective argon gas, a solution of 8.489 g (60 mmol) of chlorosulphonyl isocyanate is added dropwise, in the course of which slight exothermicity occurs. The mixture is stirred at 50° C. for 16 hours; phenol is no longer detectable by thin-layer chromatography. The mixture is heated under reflux for 16 hours; no further evolution of HCl gas takes place. The mixture is concentrated under reduced pressure, taken up in acetonitrile and admixed with aqueous acetonitrile. After stirring at room temperature for 1 hour, the mixture is concentrated, and the residue is dissolved in dichloromethane and washed with water. After drying and concentrating the organic phase, 13 g of a reaction mixture are obtained, which is chromatographed on silica gel (450 g, 40-63 μm) with dichloromethane/methanol=99/1. 1.3 g of a fraction are isolated, which consists of two components at log P=0.76 and 1.06. After separating this mixture by means of HPLC, 0.8 g of 4-amino-5-fluoro-1,2,3-benzoxathiazine 2,2-dioxide is obtained as a white solid.

Workup

  1. temperatureThe mixture is heated
  2. temperatureunder reflux for 16 hours
  3. concentrationThe mixture is concentrated under reduced pressure
  4. stirringAfter stirring at room temperature for 1 hour
  5. concentrationthe mixture is concentrated
  6. dissolutionthe residue is dissolved in dichloromethane
  7. washwashed with water
  8. customAfter drying
  9. concentrationconcentrating the organic phase, 13 g of a reaction mixture
  10. customare obtained
  11. customwhich is chromatographed on silica gel (450 g, 40-63 μm) with dichloromethane/methanol=99/1
  12. custom1.3 g of a fraction are isolated
  13. customAfter separating this mixture by means of HPLC

Sources & evidence

ORD record
ord-e8d2705f2eb24c66ab5cc0ec4e5cbc31
Source dataset
uspto-grants-2012_05
Patent number
US08173641B2

Reaction notes

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