Potassium Phosphate, Tribasic → 6-(4-Hydroxy-2-methylphenyl)benzo[d]isothiazole-3-carboxylic acid

HRID 2261815Notes

Reaction equation

HRID 2261815 reaction equation
Br[C:2]1[CH:13]=[CH:12][C:5]2[C:6]([C:9]([OH:11])=[O:10])=[N:7][S:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[OH:28])O1.[CH:30]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:28][C:23]1[CH:22]=[CH:27][C:26]([C:2]2[CH:13]=[CH:12][C:5]3[C:6]([C:9]([OH:11])=[O:10])=[N:7][S:8][C:4]=3[CH:3]=2)=[C:25]([CH3:30])[CH:24]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27346222-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 534011926-Bromobenzo(d)isothiazole-3-carboxylic acid

Product 1

HCID 1357419876-(4-Hydroxy-2-methylphenyl)benzo[d]isothiazole-3-carboxylic acidYield 273.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a degassed solution of 6-Bromo-benzo[d]isothiazole-3-carboxylic acid (0.42 g, 1.54 mmol), 3-Methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl-phenol (0.54, 2.31 mmol), 2-Dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.064 g, 0.154 mmol), and potassium phosphate (0.71 g, 3.1 mmol) in dioxane (8 mL) and water (4 mL) is added Pd(OAc)2 (6.5 mg, 0.03 mmol). The reaction is degassed again and heated to 80 degrees for 18 h. The reaction is cooled to room temperature and concentrated. The residue is diluted with EtOAc and 1N HCl. The layers are separated and concentrated. The crude material is diluted with 20 mL of MeOH and 2 mL H2SO4 and heated to reflux for 2 h. The reaction mixture is concentrated onto silica and purified by flash chromatography (20-50% EtOAc in Hexanes) to yield the title compound (0.12 g, 26%). ES/MS m/e 300.0 (M+1).

Workup

  1. customThe reaction is degassed again
  2. temperatureheated to 80 degrees for 18 h
  3. concentrationconcentrated
  4. additionThe residue is diluted with EtOAc and 1N HCl
  5. customThe layers are separated
  6. concentrationconcentrated
  7. additionThe crude material is diluted with 20 mL of MeOH and 2 mL H2SO4
  8. temperatureheated
  9. temperatureto reflux for 2 h
  10. concentrationThe reaction mixture is concentrated onto silica
  11. custompurified by flash chromatography (20-50% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-965b947aa3b74ff493bf166429e11512
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

Loading…