Iodine → Methyl 2-((4,6-difluoro-1H-indol-3-yl)thio)acetate

HRID 1621264Notes

Reaction equation

HRID 1621264 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[C:12]([O:16][CH3:17])(=[O:15])[CH2:13][SH:14].II.[I-].[K+]>CO.O>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[C:4]([S:14][CH2:13][C:12]([O:16][CH3:17])=[O:15])=[CH:5][NH:6]2

Participants

7

Reactant 4

HCID 807IodineHCID 4875Potassium IodideHCID 16907Methyl ThioglycolateHCID 27787364,6-difluoro-1H-indole

Product 1

HCID 68004081Methyl 2-((4,6-difluoro-1H-indol-3-yl)thio)acetateYield 19%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 4,6-difluoro-indole (1.00 g, 6.53 mmol) and methyl thioglycolate (584 μL, 6.53 mmol) in methanol:water (25 mL:7.0 mL) was added iodine (1.65 g, 6.53 mmol) and potassium iodide (1.09 g, 6.53 mmol). The reaction mixture was stirred at ambient temperature for 60 hours. Methanol was removed in vacuo and the aqueous layer diluted with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, evaporated in vacuo and the resulting residue was purified on a silica gel column (0-100% ethyl acetate:hexanes over 19 min) to afford the desired product (253 mg, 19% yield). LCMS>98% at 254 nm, RT=1.33 min, m/z=258 (M+1).

Workup

  1. customMethanol was removed in vacuo
  2. additionthe aqueous layer diluted with a saturated solution of sodium bicarbonate
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. customevaporated in vacuo
  6. customthe resulting residue was purified on a silica gel column (0-100% ethyl acetate:hexanes over 19 min)

Sources & evidence

ORD record
ord-e76914fa45a24e6eab541118a9d12d9d
Source dataset
uspto-grants-2014_07
Patent number
US08772509B2

Reaction notes

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