Cesium fluoride → HCID 66678410, compound

HRID 2410537Notes

Reaction equation

HRID 2410537 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[OH:12].[CH2:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O)[CH3:14].[F-].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>O1CCOCC1.CC(OC)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH2:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[OH:12])[CH3:14]

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 41008622-Ethylphenylboronic Acid (contains varying amounts of Anhydride)3×HCID 6425184Methyl 4-Bromo-3-hydroxybenzoateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl3×

Product 1

HCID 66678410HCID 66678410, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst3×HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 4-bromo-3-hydroxybenzoate (Combi-Blocks CA-4189, 3.00 g, 13.0 mmol), 2-ethylphenylboronic acid (2.92 g, 19.5 mmol), cesium fluoride (5.92 g, 39.0 mmol; 3.00), palladium acetate (58 mg, 0.26 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (320 mg, 0.78 mmol) was prepared in dioxane (30 mL) and water (15 mL) and heated at 90° C. for 2 hours. Additional amounts of 2-ethylphenylboronic acid (1.46 g, 9.7 mmol), palladium acetate (58 mg, 0.26 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (320 mg, 0.78 mmol) were added, and the mixture was stirred for 2 additional hours. Additional amounts of 2-ethylphenylboronic acid (0.73 g, 4.9 mmol), palladium acetate (29 mg, 0.13 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (160 mg, 0.39 mmol) were added, and the mixture was stirred for 2 additional hours. The reaction mixture was diluted with MTBE (150 mL), and then washed with water (50 mL) and brine (50 mL). The aqueous layers were extracted with MTBE (75 mL). The organic layers were combined, dried (MgSO4) and concentrated under vacuum. After purification by flash chromatography (silica, heptane/EtOAc), the title compound was obtained as a yellow oil (3.13 g, 94%). HPLC (Method A) Rt 4.5 min (Purity: 99.2%). LC/MS (Method B): 255.1 (M−H)−.

Workup

  1. stirringthe mixture was stirred for 2 additional hours
  2. washwashed with water (50 mL) and brine (50 mL)
  3. extractionThe aqueous layers were extracted with MTBE (75 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under vacuum
  6. customAfter purification by flash chromatography (silica, heptane/EtOAc)

Sources & evidence

ORD record
ord-27fecf1109bb4e058bb86d69c53e8b57
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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