Hydrogen Peroxide → 3-(3-Fluoro-4-methoxyphenyl)isothiazol-5-ylamine

HRID 2422710Notes

Reaction equation

HRID 2422710 reaction equation
OO.[NH2:3][C:4]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([F:17])[CH:10]=1)=[CH:5][C:6]([NH2:8])=[S:7]>CO>[F:17][C:11]1[CH:10]=[C:9]([C:4]2[CH:5]=[C:6]([NH2:8])[S:7][N:3]=2)[CH:14]=[CH:13][C:12]=1[O:15][CH3:16]

Participants

4

Reactant 2

HCID 784Hydrogen PeroxideHCID 866326523-Amino-3-(3-fluoro-4-methoxyphenyl)thioacrylamide

Product 1

HCID 671815313-(3-Fluoro-4-methoxyphenyl)isothiazol-5-ylamineYield 12.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Add hydrogen peroxide (30% in water, 8.73 g, 257 mmol) to 3-amino-3-(3-fluoro-4-methoxyphenyl)-thioacrylamide (29.0 g, 128 mmol) in methanol (1,283 mL) and stir the reaction mixture at room temperature. Quench the reaction with Na2S2O3 (20% in water) and concentrate to dryness. Dilute with EtOAc (900 mL) and water (900 mL), collect the organic phase, and evaporate. Crystallize from EtOAc/hexanes to afford 3-(3-fluoro-4-methoxyphenyl)isothiazol-5-ylamine (1 g). Chromatography of the mother liquor (25 g) over silica gel, eluting with 25-50% EtOAc in hexane, affords additional product. [In one instance, a column loading accident led to loss of ½ of the material; but additional clean material was recovered from the chromatography (1 g).] Yield: 12.2%. ES-MS: m/e 225.0 (m+1).

Workup

  1. customQuench
  2. customthe reaction with Na2S2O3 (20% in water)
  3. concentrationconcentrate to dryness
  4. additionDilute with EtOAc (900 mL) and water (900 mL)
  5. customcollect the organic phase
  6. customevaporate
  7. customCrystallize from EtOAc/hexanes

Sources & evidence

ORD record
ord-a53525d5113f4f87a358a987844bc37b
Source dataset
uspto-grants-2011_06
Patent number
US07960419B2

Reaction notes

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