Water → Methyl 3'-fluoro-2-(methoxymethyl)-2'-methylbiphenyl-4-carboxylate

HRID 1630999Notes

Reaction equation

HRID 1630999 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].[F:15][C:16]1[C:17]([CH3:25])=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1.[F-].[Cs+].O>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>[F:15][C:16]1[C:17]([CH3:25])=[C:18]([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:19]=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 27831913-Fluoro-2-methylphenylboronic AcidHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoate

Product 1

HCID 58554131Methyl 3'-fluoro-2-(methoxymethyl)-2'-methylbiphenyl-4-carboxylate

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 4-bromo-3-(methoxymethyl)benzoate (5.00 g, 19.3 mmol), 3-fluoro-2-methylphenylboronic acid (Combi-Blocks BB-3475, 4.46 g, 29.0 mmol), bis(triphenylphosphine)palladium(II) chloride (271 mg, 0.39 mmol) and cesium fluoride (8.79 g, 57.9 mmol) was prepared in dioxane (50 mL) and water (20 mL) under N2 atmosphere. The reaction mixture was heated at 100° C. for 1 hour. The reaction mixture was cooled at RT, diluted with MTBE (250 mL) and the layers were separated. The organic layer was washed with water (100 mL) and brine (100 mL). The aqueous layers were extracted with MTBE (150 mL). The organic layers were combined, dried (MgSO4) and concentrated under reduced pressure. After purification by flash chromatography (silica, EtOAc/n-hexane), the title compound was obtained as a colorless oil (4.85 g, 87%). HPLC (Method A), Rt: 5.0 min (purity: 99.5%). UPLC/MS, M+(ESI): 289.0.

Workup

  1. temperatureThe reaction mixture was cooled at RT
  2. customthe layers were separated
  3. washThe organic layer was washed with water (100 mL) and brine (100 mL)
  4. extractionThe aqueous layers were extracted with MTBE (150 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification by flash chromatography (silica, EtOAc/n-hexane)

Sources & evidence

ORD record
ord-b1b5ab17e4b349daab951182c855564e
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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