Cesium carbonate → Methyl 4-(5,6-dimethoxy-3-pyridyl)-2,6-dimethylbenzoate

HRID 1259340Notes

Reaction equation

HRID 1259340 reaction equation
[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6](B2OC(C)(C)C(C)(C)O2)=[CH:5][N:4]=1.Br[C:21]1[CH:30]=[C:29]([CH3:31])[C:24]([C:25]([O:27][CH3:28])=[O:26])=[C:23]([CH3:32])[CH:22]=1.C([O-])([O-])=O.[Cs+].[Cs+].CCOC(C)=O.O>CS(C)=O.CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:10][O:9][C:8]1[CH:7]=[C:6]([C:21]2[CH:30]=[C:29]([CH3:31])[C:24]([C:25]([O:27][CH3:28])=[O:26])=[C:23]([CH3:32])[CH:22]=2)[CH:5]=[N:4][C:3]=1[O:2][CH3:1]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 22728543Water ethylacetateHCID 23134395Methyl 4-bromo-2,6-diMethylbenzoateHCID 453617702,3-Dimethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine2×

Product 1

HCID 66743002Methyl 4-(5,6-dimethoxy-3-pyridyl)-2,6-dimethylbenzoateYield 29.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

As shown in step 6-i of Scheme 6, 2,3-dimethoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Compound 2021, 920 mg, 3.47 mmol), methyl 4-bromo-2,6-dimethyl-benzoate (844 mg, 3.47 mmol), and Cs2CO3 (2.26 g, 6.94 mmol) were taken up in DMSO (12 mL) in a sealable tube. Nitrogen gas was bubbled through the solution for 5 minutes, dppfPdCl2 (141 mg, 0.174 mmol) added, and the vessel sealed. The reaction mixture was heated at 90° C. for 60 minutes under an atmosphere of nitrogen. After cooling, the mixture was poured into EtOAc/water. The organics were washed with water, brine, passed through a plug of Florisil®, and concentrated under reduced pressure to give a solid. The solid was suspended in MeOH and collected by filtration to provide methyl 4-(5,6-dimethoxy-3-pyridyl)-2,6-dimethyl-benzoate (Compound 2022, 310 mg). The filtrate was concentrated and purified by silica gel chromatography (0 to 50% EtOAc/hex) to provide an additional 400 mg of Compound 2022 (total yield 710 mg, 2.4 mmol, 68% yield). This compound was used in subsequent reactions as is.

Workup

  1. customNitrogen gas was bubbled through the solution for 5 minutes
  2. customthe vessel sealed
  3. temperatureAfter cooling
  4. washThe organics were washed with water, brine
  5. concentrationconcentrated under reduced pressure
  6. customto give a solid
  7. filtrationcollected by filtration

Sources & evidence

ORD record
ord-5773698d9e72455fb194b2ed2950be1f
Source dataset
uspto-grants-2013_06
Patent number
US08466288B2

Reaction notes

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