Water → 4-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]benzoic Acid

HRID 1797177Notes

Reaction equation

HRID 1797177 reaction equation
[F:1][C:2]([C:12]1[CH:17]=[CH:16][C:15](I)=[CH:14][CH:13]=1)([CH3:11])[CH2:3][NH:4][S:5]([CH:8]([CH3:10])[CH3:9])(=[O:7])=[O:6].[C:19]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)([OH:21])=[O:20].C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.O>[F:1][C:2]([C:12]1[CH:17]=[CH:16][C:15]([C:25]2[CH:26]=[CH:27][C:22]([C:19]([OH:21])=[O:20])=[CH:23][CH:24]=2)=[CH:14][CH:13]=1)([CH3:11])[CH2:3][NH:4][S:5]([CH:8]([CH3:10])[CH3:9])(=[O:7])=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 9800265[2-Fluoro-2-(4-iodophenyl)propyl][(methylethyl)sulfonyl]amine

Product 1

HCID 221765834-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]benzoic AcidYield 31%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

Scheme VI, Step A′: Into a 50 mL single neck flask [2-fluoro-2-(4-iodophenyl)propyl][(methylethyl)sulfonyl]amine (300 mg, 0.78 mmol, prepared in example 1), 4-carboxybenzene boronic acid (188 mg, 1.13 mmol), potassium carbonate (156 mg, 1.13 mmol) and tetrakis(triphenyl phosphine)palladium(0) (52 mg, 0.05 mmol) were combined in dioxane/water (30 mL, 3:1). The mixture was then heated at 100° C. with stirring for 18 hours. The reaction was cooled to room temperature and poured into H2O. The desired product was extracted with ethyl acetate and the organic layer was separated, washed twice with H2O, dried over K2CO3, and concentrated under reduced vacuum to yield the crude material (350 mg) as a tan solid. The crude material was purified via silica gel chromatography employing the Chromatotron using a 4000 micron rotor and eluting with a solvent of methylene chloride/methanol 9:1 to yield the title compound (91 mg, 31%) as a white solid.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionThe desired product was extracted with ethyl acetate
  3. customthe organic layer was separated
  4. washwashed twice with H2O
  5. dry with materialdried over K2CO3
  6. concentrationconcentrated under reduced vacuum
  7. customto yield the crude material (350 mg) as a tan solid
  8. customThe crude material was purified via silica gel chromatography
  9. washeluting with a solvent of methylene chloride/methanol 9:1

Sources & evidence

ORD record
ord-2b39fd69abca49158e8a8586426b32f2
Source dataset
uspto-grants-2006_04
Patent number
US07034045B1

Reaction notes

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