Water → Methyl 4-(4-methoxyphenyl)-3-methylbenzoate

HRID 1508558Notes

Reaction equation

HRID 1508558 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=1[CH3:23].C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=2[CH3:23])=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 3294148Methyl 4-bromo-3-methylbenzoate

Product 1

HCID 67065985Methyl 4-(4-methoxyphenyl)-3-methylbenzoate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 10000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen was placed a solution of (4-methoxyphenyl)boronic acid (350 g, 2.30 mol, 1.00 equiv) in 1,4-dioxane (3500 mL), methyl 4-bromo-3-methylbenzoate (527 g, 2.30 mol, 1.00 equiv), Pd(PPh3)4 (79.8 g, 69.06 mmol, 0.03 equiv), Cs2CO3 (1501 g, 4.60 mol, 2.00 equiv), water (850 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The reaction was then cooled and quenched by the addition of 3000 mL of water. The resulting solution was extracted with 2×2000 mL of ethyl acetate. The organic layers were combined, washed with 1×2000 mL of brine, dried and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:50-1:20). This resulted in 471.6 g (crude) of methyl 4-(4-methoxyphenyl)-3-methylbenzoate as a red solid.

Workup

  1. customInto a 10000-mL 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureThe reaction was then cooled
  4. customquenched by the addition of 3000 mL of water
  5. extractionThe resulting solution was extracted with 2×2000 mL of ethyl acetate
  6. washwashed with 1×2000 mL of brine
  7. customdried
  8. concentrationconcentrated under vacuum
  9. washeluted with ethyl acetate/petroleum ether (1:50-1:20)
  10. customThis resulted in 471.6 g (crude) of methyl 4-(4-methoxyphenyl)-3-methylbenzoate as a red solid

Sources & evidence

ORD record
ord-2a48ee03a4524cbfac7518a8c8b1a70c
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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