2-Fluoro-4-iodoaniline → 7-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid tert-butyl ester

HRID 79031Notes

Reaction equation

HRID 79031 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:16]=[CH:15][C:11]2[CH:12]=[N:13][S:14][C:10]=2[C:9]=1F)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:18][C:19]1[CH:24]=[C:23]([I:25])[CH:22]=[CH:21][C:20]=1[NH2:26].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[C:1]([O:5][C:6]([C:8]1[CH:16]=[CH:15][C:11]2[CH:12]=[N:13][S:14][C:10]=2[C:9]=1[NH:26][C:20]1[CH:21]=[CH:22][C:23]([I:25])=[CH:24][C:19]=1[F:18])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium HexamethyldisilazideHCID 575231267-Fluoro-benzo[d]isothiazole-6-carboxylic acid tert-butyl ester

Product 1

HCID 575215037-(2-Fluoro-4-iodo-phenylamino)-benzo[d]isothiazole-6-carboxylic acid tert-butyl esterYield 30.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-fluoro-benzo[d]isothiazole-6-carboxylic acid tert-butyl ester (1.26 g, 5.0 mmol) and 2-fluoro-4-iodo-phenylamine (1.18 g, 5.0 mmol) in anhydrous THF (25 mL) at −78° C. was added a 1.0M solution of LHMDS in hexanes (10.0 mL, 10.0 mmol) under a nitrogen atmosphere. The reaction mixture was allowed to warm to room temperature and then stirred for 30 minutes before being quenched by the addition of a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was separated and washed with water followed by brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was subjected to flash chromatography (Si—PPC, gradient 0% to 10%, TBME in cyclohexane) to give the title compound as a yellow solid (717 mg, 30%). LCMS (method B): RT=5.14 min, [M+H]+=471.

Workup

  1. custombefore being quenched by the addition of a saturated aqueous solution of ammonium chloride
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-efb263d1f3bb412c8f45bddb293129d3
Source dataset
uspto-grants-2014_09
Patent number
US08841462B2

Reaction notes

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