Potassium Phosphate, Tribasic → HCID 67409967, compound

HRID 515216Notes

Reaction equation

HRID 515216 reaction equation
[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:26])=[O:25].Cl[C:29]1[CH:36]=[C:35]([OH:37])[CH:34]=[CH:33][C:30]=1[C:31]#[N:32].P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>O1CCOCC1.O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1([F:27])[CH2:4][CH:3]1[CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:29]3[CH:36]=[C:35]([OH:37])[CH:34]=[CH:33][C:30]=3[C:31]#[N:32])=[CH:14][C:9]=2[N:8]([CH3:24])[S:7]1(=[O:25])=[O:26]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 5927972-Chloro-4-hydroxybenzonitrileHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 67413064HCID 67413064, compound

Product 1

HCID 67409967HCID 67409967, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (12-1) (2.0 g, 5.0 mmol, 1 eq), 2-chloro-4-hydroxybenzonitrile (0.84 g, 5.5 mmol, 1.1 eq), tripotassium phosphate (2.1 g, 10.0 mmol, 2.0 eq), S-Phos (0.20 g, 0.5 mmol, 0.1 eq), and palladium(II) acetate (56 mg, 0.25 mmol, 0.05 eq) were combined in dioxane (20 mL) and water (3 mL). The resulting mixture was heated at 100° C. for 16 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (100 mL), washed with water (20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (80 g SiO2, 0-80% EtOAc in hexanes) to afford 2-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro-2,1,3-benzothiadiazol-5-yl}-4-hydroxybenzonitrile (12-2) as a white solid. LRMS m/z (M+H) 392.3 found, 392.1 required.

Workup

  1. temperatureto cool to room temperature
  2. washwashed with water (20 mL) and brine (20 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash chromatography (80 g SiO2, 0-80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-77d9c800d13a42228e348ac7afb6a0b2
Source dataset
uspto-grants-2015_08
Patent number
US09108937B2

Reaction notes

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