Potassium Iodide → HCID 67468126, compound

HRID 1845912Notes

Reaction equation

HRID 1845912 reaction equation
N[C:2]1[CH:17]=[CH:16][C:5]2[N:6]([CH2:10][CH:11]3[CH2:13][C:12]3([F:15])[F:14])[C:7](=[O:9])[S:8][C:4]=2[C:3]=1[Br:18].[I-:19].[K+].O.CC1C=CC(S(O)(=O)=O)=CC=1.N([O-])=O.[Na+]>O.CCOC(C)=O.O1CCOCC1>[Br:18][C:3]1[C:4]2[S:8][C:7](=[O:9])[N:6]([CH2:10][CH:11]3[CH2:13][C:12]3([F:15])[F:14])[C:5]=2[CH:16]=[CH:17][C:2]=1[I:19]

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 521998p-Toluenesulfonic acid monohydrateHCID 23668193Sodium NitriteHCID 67468447HCID 67468447, compound

Product 1

HCID 67468126HCID 67468126, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a round bottom flask was added 6-amino-7-bromo-3-[(2,2-difluorocyclopropyl)methyl]-1,3-benzothiazol-2(3H)-one (13-3) (0.205 g, 0.612 mmol), Dioxane (2.5 mL), water (2.0 mL), potassium iodide (1.015 g, 6.12 mmol), and 4-methylbenzenesulfonic acid hydrate (0.349 g, 1.835 mmol), then dropwise addition of a solution of sodium nitrite (0.084 g, 1.223 mmol) in water (0.5 mL). Reaction mixture was then stirred at room temperature for a few hours, then heated to 75 C in a hot oil bath with stirring overnight (˜15 hours). The reaction mixture was then cooled to room temperature then suspended in EtOAc, washed with sat'd Na2S2O3, then with sat'd NaHCO3, then water, then brine. Organics were then dried over Na2SO4 filtered & concentrated. Purification of crude reaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 40% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water) gave 7-bromo-3-[(2,2-difluorocyclopropyl)methyl]-6-iodo-1,3-benzothiazol-2(3H)-one (13-4) as a pink solid. HRMS (M+H)+: observed=445.852, calculated=445.8517.

Workup

  1. customReaction mixture
  2. temperatureheated to 75 C in a hot oil bath
  3. stirringwith stirring overnight (˜15 hours)
  4. temperatureThe reaction mixture was then cooled to room temperature
  5. washwashed with sat'd Na2S2O3
  6. dry with materialOrganics were then dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of crude
  10. customreaction mixture by reverse phase chromatography (Waters Sunfire MSC18, 40% acetonitrile/0.1% trifluoroacetic acid/water→100% acetonitrile/0.1% trifluoroacetic acid/water)

Sources & evidence

ORD record
ord-74acbc8b05aa4166bc26a1642bce29b0
Source dataset
uspto-grants-2015_02
Patent number
US08952005B2

Reaction notes

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