Cesium fluoride → HCID 66678157, compound

HRID 2410532Notes

Reaction equation

HRID 2410532 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[CH2:12][O:13][CH3:14].FC1C(C)=C(C2C=CC(C(O)=O)=CC=2COC)C=CC=1.[F:35][C:36]1[CH:37]=[CH:38][C:39]([CH3:45])=[C:40](B(O)O)[CH:41]=1.[F-].[Cs+]>O1CCOCC1.CC(OC)(C)C.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.O>[F:35][C:36]1[CH:41]=[CH:40][C:39]([CH3:45])=[C:38]([C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=2[CH2:12][O:13][CH3:14])[CH:37]=1

Participants

9

Reactant 4

HCID 25953Cesium fluorideHCID 27831905-Fluoro-2-methylphenylboronic acidHCID 580663983'-Fluoro-2-(methoxymethyl)-2'-methylbiphenyl-4-carboxylic acidHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoate

Product 1

HCID 66678157HCID 66678157, compound

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 4-bromo-3-(methoxymethyl)benzoate (Intermediate 1, Step 2, 3.00 g, 11.6 mmol), 5-fluoro-2-methylphenylboronic acid (2.67 g, 17.4 mmol), bis(triphenylphosphine)palladium(II) chloride (162 mg, 0.23 mmol) and cesium fluoride (5.28 g, 34.7 mmol) was prepared in dioxane (30 mL) and water (12 mL) under nitrogen atmosphere. The reaction mixture was heated at 90° C. for 3 hours. The reaction mixture was cooled at RT, diluted with MTBE (150 mL) and the layers were separated. The organic layer was washed with brine (50 mL). The aqueous layers were extracted with MTBE (100 mL). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure. After purification by flash chromatography (silica, EtOAc/heptane), the title compound was obtained as a colorless oil (2.88 g, 86%). HPLC (Method A), Rt 5.0 min (purity: 98.7%). LC/MS (Method B): 288.9 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled at RT
  2. customthe layers were separated
  3. washThe organic layer was washed with brine (50 mL)
  4. extractionThe aqueous layers were extracted with MTBE (100 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification by flash chromatography (silica, EtOAc/heptane)

Sources & evidence

ORD record
ord-d5d3b718a79f47e68e75f548aaead7ef
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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