2-Chloro-4-iodoaniline → HCID 9871667, compound

HRID 353054Notes

Reaction equation

HRID 353054 reaction equation
[Cl:1][C:2]1[CH:8]=[C:7]([I:9])[CH:6]=[CH:5][C:3]=1[NH2:4].C([N-]C(C)C)(C)C.[Li+].[CH3:18][O:19][C:20](=[O:36])[C:21]1[CH:26]=[C:25]([S:27](=[O:32])(=[O:31])[N:28]([CH3:30])[CH3:29])[C:24]([F:33])=[C:23]([F:34])[C:22]=1F>O1CCCC1>[CH3:18][O:19][C:20](=[O:36])[C:21]1[CH:26]=[C:25]([S:27](=[O:32])(=[O:31])[N:28]([CH3:30])[CH3:29])[C:24]([F:33])=[C:23]([F:34])[C:22]=1[NH:4][C:3]1[CH:5]=[CH:6][C:7]([I:9])=[CH:8][C:2]=1[Cl:1]

Participants

5

Reactant 3

HCID 2829302-Chloro-4-iodoanilineHCID 2724682Lithium diisopropylamideHCID 12050375HCID 12050375, compound

Product 1

HCID 9871667HCID 9871667, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring cold (−78° C.) solution comprised of 2-chloro-4-iodoaniline (0.143 g, 5.64×10−4 mol) in anhydrous tetrahydrofuran (5 ml) under a nitrogen atmosphere was added a commercially available lithium diisopropylamide solution (Aldrich, 2.0 M in tetrahydrofuran/heptane/ethylbenzene, 0.300 ml, 6.0×10−4 mol). After stirring for 5 minutes, a solution comprised of 5-dimethylsulfamoyl-2,3,4-trifluoro-benzoic acid methyl ester (0.15 g, 5.0×10−4 mol) in tetrahydrofuran (10 ml) was added via syringe. The cold bath was removed and the reaction mixture was stirred for 2 hours. The reaction mixture was then partitioned between diethyl ether (125 ml) and saturated aqueous sodium bicarbonate (125 ml). The aqueous bicarbonate phase was extracted with an additional portion (125 ml) of diethyl ether. The combined organic phases were dried over anhydrous magnesium sulfate and concentrated in vacuo to give a yellow oil. The oil was crystallized from heptane-ethyl acetate to afford 0.060 g of an off-white powder; 23% yield; mp 154-156° C.; 1H-NMR (400 MHz; CDCl3) δ9.74 (s, 1H), 8.30 (d, 1H, J=7.1 Hz), 7.72 (s, 1H), 7.49 (d, 1H, J=8.3 Hz), 6.73-6.69 (m, 1H), 3.92 (s, 3H), 2.84 (s, 3H), 2.83 (s, 3H); 19F-NMR (376 MHz; CDCl3) δ−123.90 (d), −139.55 (d).

Workup

  1. customTo a stirring cold (−78° C.) solution
  2. additionwas added via syringe
  3. customThe cold bath was removed
  4. stirringthe reaction mixture was stirred for 2 hours
  5. customThe reaction mixture was then partitioned between diethyl ether (125 ml) and saturated aqueous sodium bicarbonate (125 ml)
  6. extractionThe aqueous bicarbonate phase was extracted with an additional portion (125 ml) of diethyl ether
  7. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give a yellow oil
  10. customThe oil was crystallized from heptane-ethyl acetate

Sources & evidence

ORD record
ord-0ca4654ec348448fbed01d13d103abc2
Source dataset
uspto-grants-2004_06
Patent number
US06750217B2

Reaction notes

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