Triethylamine → {2-[(2-Tert-butyl-1,1-dioxido-3-oxo-2,3-dihydro-1,2-benzisothiazol-6-yl)ethynyl]-4-chlorophenoxy}acetic acid

HRID 2390373Notes

Reaction equation

HRID 2390373 reaction equation
[Cl:1][C:2]1[CH:12]=[CH:11][C:5]([O:6][CH2:7][C:8]([OH:10])=[O:9])=[C:4]([C:13]#[CH:14])[CH:3]=1.Br[C:16]1[CH:31]=[CH:30][C:19]2[C:20](=[O:29])[N:21]([C:25]([CH3:28])([CH3:27])[CH3:26])[S:22](=[O:24])(=[O:23])[C:18]=2[CH:17]=1.C(N(CC)CC)C.CCOC(C)=O>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:25]([N:21]1[C:20](=[O:29])[C:19]2[CH:30]=[CH:31][C:16]([C:14]#[C:13][C:4]3[CH:3]=[C:2]([Cl:1])[CH:12]=[CH:11][C:5]=3[O:6][CH2:7][C:8]([OH:10])=[O:9])=[CH:17][C:18]=2[S:22]1(=[O:23])=[O:24])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 58522016(4-Chloro-2-ethynylphenoxy)acetic acid2×HCID 670084406-bromo-2-tert-butyl-1,2-benzisothiazol-3(2H)-one-1,1-dioxide

Product 1

HCID 46865414{2-[(2-Tert-butyl-1,1-dioxido-3-oxo-2,3-dihydro-1,2-benzisothiazol-6-yl)ethynyl]-4-chlorophenoxy}acetic acid

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (4-chloro-2-ethynylphenoxy)acetic acid (Intermediate 238; 211 mg; 1.00 mmol), 6-bromo-2-tert-butyl-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (prepared as described in Tetrahedron, 2006, 62, 7902-7910, 382 mg; 1.20 mmol), dichlorobis(triphenylphosphine)palladium(II) (70 mg; 0.10 mmol) and cuprous iodide (9.5 mg; 0.05 mmol) in anhydrous THF (4 ml) was degassed for 10 minutes then treated with triethylamine (1.00 ml; 7.21 mmol) and the mixture stirred at 60° C. for 16 h. EtOAc was added and the organic phase washed with a sat. NH4Cl solution then brine. The organic phase was dried on MgSO4, filtered and concentrated under reduced pressure to give a residue which was purified by preparative HPLC to afford the title compound as a white solid.

Workup

  1. customwas degassed for 10 minutes
  2. washthe organic phase washed with a sat. NH4Cl solution
  3. customThe organic phase was dried on MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto give a residue which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-6ead0710e29f4fb09324ae96d1b6626a
Source dataset
uspto-grants-2012_09
Patent number
US08273769B2

Reaction notes

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