Hydrogen Peroxide → HCID 57998863, compound

HRID 509076Notes

Reaction equation

HRID 509076 reaction equation
OO.[F:3][CH:4]([F:29])[S:5]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[F:17])[C:10]([C:18]2[N:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([O:26][CH3:27])[N:19]=2)=C1O)(=[O:7])=[O:6].C(=O)([O-])[OH:31].[K+].N1C=CC=CC=1C(O)=O.S([O-])([O-])=O.[Na+].[Na+]>O.C(#N)C.C(#N)C.O.S([O-])([O-])(=O)=O.[Fe+2].O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2]>[CH3:27][O:26][C:20]1[N:21]=[C:22]([O:24][CH3:25])[N:23]=[C:18]([C:10]([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]([F:17])[C:16]=2[NH:8][S:5]([CH:4]([F:29])[F:3])(=[O:7])=[O:6])=[O:31])[N:19]=1

Participants

11

Reactant 5

HCID 784Hydrogen Peroxide2×HCID 1018Picolinic acidHCID 24437Sodium SulfiteHCID 516893Potassium Bicarbonate2×HCID 1363382311-[(Difluoromethyl)sulfonyl]-3-(4,6-dimethoxy-1,3,5-triazin-2-yl)-7-fluoro-1H-indol-2-ol

Product 1

HCID 57998863HCID 57998863, compound

Reagents, catalysts & solvents 5

HCID 24393Ferrous SulfateCatalystHCID 62662Ferrous sulfate heptahydrateCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
35 °C

Procedure

Variant A (Oxidation with Hydrogen Peroxide and Iron Sulfate in Water/Acetonitrile): 1-[(Difluoromethyl)sulfonyl]-3-(4,6-dimethoxy-1,3,5-triazin-2-yl)-7-fluoro-1H-indol-2-ol (100 g) is initially charged in 330 ml of acetonitrile and the suspension is heated to 35° C. A solution of potassium hydrogencarbonate (25.4 g) in 145 ml of water is added dropwise within 45 min. Iron(II) sulfate heptahydrate (395 mg) and pyridine-2-carboxylic acid (175 mg) are premixed in 1 ml of water and added to the mixture. Hydrogen peroxide (35% in water, 58 g) is added dropwise over 135 min, and the internal temperature is kept at 25° C.-28° C. Stirring is continued for 170 min, sodium sulfite (3 g) and potassium hydrogencarbonate (3 g) is added, the mixture is concentrated to 282 g at 40° C. under reduced pressure, and the solid residue is filtered off. 2-Propanol (150 ml) is added to the solution and the pH is adjusted to 2 with hydrochloric acid, such that a solid precipitates out. After adding 160 ml of water, the solid is filtered off, washed with 100 ml of 2-propanol/water (1:4) and 200 ml of water, and dried. This gives N-{2-[(4,6-dimethoxy-1,3,5-triazin-2-yl)carbonyl]-6-fluorophenyl}-1,1-difluoromethanesulfonamide in a purity of 97% (86.2 g, 90% of theory).

Workup

  1. additionadded to the mixture
  2. customis kept at 25° C.-28° C
  3. concentrationthe mixture is concentrated to 282 g at 40° C. under reduced pressure
  4. filtrationthe solid residue is filtered off
  5. addition2-Propanol (150 ml) is added to the solution
  6. customprecipitates out
  7. additionAfter adding 160 ml of water
  8. filtrationthe solid is filtered off
  9. washwashed with 100 ml of 2-propanol/water (1:4) and 200 ml of water
  10. customdried

Sources & evidence

ORD record
ord-70d4a024438844fab1075a0d5f7f38d9
Source dataset
uspto-grants-2015_08
Patent number
US09096551B2

Reaction notes

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