Ethanol → 2',3',4'-Trimethoxy-biphenyl-3-carboxylic acid methyl ester

HRID 383586Notes

Reaction equation

HRID 383586 reaction equation
N#N.[CH3:3][O:4][C:5]1[C:10]([O:11][CH3:12])=[C:9]([O:13][CH3:14])[CH:8]=[CH:7][C:6]=1B(O)O.CCO.[CH3:21][O:22][C:23](=[O:31])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=1>C1(C)C=CC=CC=1.O.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>[CH3:21][O:22][C:23]([C:24]1[CH:25]=[C:26]([C:6]2[CH:7]=[CH:8][C:9]([O:13][CH3:14])=[C:10]([O:11][CH3:12])[C:5]=2[O:4][CH3:3])[CH:27]=[CH:28][CH:29]=1)=[O:31]

Participants

8

Reactant 4

HCID 702EthanolHCID 947NitrogenHCID 12070Methyl 3-bromobenzoateHCID 27735822,3,4-Trimethoxybenzeneboronic acid

Product 1

HCID 161162902',3',4'-Trimethoxy-biphenyl-3-carboxylic acid methyl esterYield 59%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

(The following reaction is done in an N2 atmosphere.) To a solution of 2,3,4-Trimethoxyphenylboronic acid (42) (1.40 g, 6.60 mmol) in toluene (15.0 mL) is added EtOH (2.0 mL), Pd(PPh3)4 (208 mg, 0.18 mmol) and Na2CO3.10H2O (4.81 g, 16.80 mmol) in water (5.2 mL). The resulting mixture is carefully degassed (5 times alternating vacuum and flushing with N2). A solution of Methyl-3-bromobenzoate (11) (1.29 g, 6.00 mmol) in toluene (9.0 mL) is added by syringe, the resulting mixture is again carefully degassed and stirred overnight at 100° C. Partition the mixture between brine/EtOAc (1+1), separate layers, extract the aqu. layer with EtOAc (3×), wash the combined organic layer with brine, dry with Na2SO4 and remove solvent. Purify crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+5) to obtain 2′,3′,4′-Trimethoxy-biphenyl-3-carboxylic acid methyl ester (43) as a yellowish oil (1.07 g, 58%). 1H NMR (400 MHz, CDCl3): 3.66 (s, 3H); 3.89 (s, 3H); 3.92 (s, 6H); 6.74 (d, 1H, J=8.6 Hz); 7.03 (d, 1H, J=8.6 Hz); 7.44 (t, 1H, J=7.8 Hz); 7.70 (d, 1H, J=7.6 Hz); 7.97 (d, 1H, J=7.8 Hz); 8.15 (br.s 1H).

Workup

  1. custom(The following reaction
  2. customThe resulting mixture is carefully degassed
  3. custom(5 times alternating vacuum and flushing with N2)
  4. customthe resulting mixture is again carefully degassed
  5. customPartition the mixture between brine/EtOAc (1+1)
  6. customseparate layers
  7. extractionextract the aqu
  8. washlayer with EtOAc (3×), wash the combined organic layer with brine
  9. dry with materialdry with Na2SO4
  10. customremove solvent
  11. customPurify crude product by preparative radial chromatography (silica gel, EtOAc/CyH 1+5)

Sources & evidence

ORD record
ord-d2feca733bc842d59da79f1cc8b24508
Source dataset
uspto-grants-2013_02
Patent number
US08367677B2

Reaction notes

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