Hydrochloric Acid → N-(4-Iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amine

HRID 9587

Reaction equation

HRID 9587 reaction equation
Cl[C:2]1[S:3][C:4]2[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:5]=2[N:6]=1.[F:12][C:13]1[CH:19]=[C:18]([I:20])[CH:17]=[CH:16][C:14]=1[NH2:15].Cl>C(O)CCC>[I:20][C:18]1[CH:17]=[CH:16][C:14]([NH:15][C:2]2[S:3][C:4]3[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:5]=3[N:6]=2)=[C:13]([F:12])[CH:19]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 771762,6-Dichlorobenzothiazole2×HCID 1856942-Fluoro-4-iodoaniline

Product 1

HCID 23549325N-(4-Iodo-2-fluorophenyl)-6-chloro-1,3-benzothiazol-2-amineYield 38%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2,6-dichlorobenzothiazole (1.0 g, 4.9 mmol) and 2-fluoro-4-iodoaniline (2.32 g, 9.8 mmol) in 20 mL BuOH was stirred at 90° C., and then HCl (4 M in dioxane, 1.0 mL) was added. The reaction mixture was stirred with heating at 90° C. overnight, under argon. NMR analysis then showed little 2,6-dichlorobenzothiazole remaining. After BuOH was removed by rotary evaporation, EtOAc (100 mL) and 1 N aqueous HCl (100 mL) were added. The organic layer was separated and washed with 1 N aqueous HCl (100 mL), saturated Na2O2S3 solution (50 mL), water (100 mL), and then dried over Na2SO4. Removal of solvent under reduced pressure afforded a residue, which was triturated with EtOAc (10 mL) and hexanes (40 mL). The solid was filtered and dried in vacuo to a constant weight, to afford the desired product as a light purple solid (0.75 g, 38%). 1H NMR (DMSO-d6) δ 10.45 (s, 1H), 8.35 (t, 1H), 7.95 (s, 1H), 7.70 (d, 1H), 7.58 (d, 2H), 7.30 (d, 1H).

Workup

  1. stirringThe reaction mixture was stirred
  2. temperaturewith heating at 90° C. overnight, under argon
  3. customAfter BuOH was removed by rotary evaporation, EtOAc (100 mL) and 1 N aqueous HCl (100 mL)
  4. additionwere added
  5. customThe organic layer was separated
  6. washwashed with 1 N aqueous HCl (100 mL), saturated Na2O2S3 solution (50 mL), water (100 mL)
  7. dry with materialdried over Na2SO4
  8. customRemoval of solvent under reduced pressure
  9. customafforded a residue, which
  10. customwas triturated with EtOAc (10 mL) and hexanes (40 mL)
  11. filtrationThe solid was filtered
  12. customdried in vacuo to a constant weight

Sources & evidence

ORD record
ord-9d138c95ab1b4327808ade8f930cea49
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Linked notes

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