Nitrogen → 3',4',5'-Trimethoxy-biphenyl-2-carboxylic acid methyl ester

HRID 2075935Notes

Reaction equation

HRID 2075935 reaction equation
N#N.[CH3:3][O:4][C:5](=[O:13])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1Br.[CH3:14][O:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[C:20]([O:24][CH3:25])[C:21]=1[O:22][CH3:23]>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>[CH3:3][O:4][C:5]([C:6]1[C:7]([C:18]2[CH:19]=[C:20]([O:24][CH3:25])[C:21]([O:22][CH3:23])=[C:16]([O:15][CH3:14])[CH:17]=2)=[CH:8][CH:9]=[CH:10][CH:11]=1)=[O:13]

Participants

7

Reactant 3

HCID 947NitrogenHCID 11894Methyl 2-bromobenzoateHCID 27343903,4,5-Trimethoxybenzeneboronic acid

Product 1

HCID 597857033',4',5'-Trimethoxy-biphenyl-2-carboxylic acid methyl esterYield 100.2%

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 Methyl-2-bromobenzoate (53) (922 mg, 4.29 mmol) in toluene (11 mL) is added Pd(PPh3)4 (297 mg, 0.26 mmol) and Na2CO3.10H2O (3.43 g, 12.00 mmol) in water (3.8 mL). Degas the resulting mixture is carefully (5 times alternating vacuum and flushing with N2). Add a solution of 3,4,5-Trimethoxyphenylboronic acid (54) (1.00 g, 4.72 mmol) in toluene (10 mL) by syringe, degas the resulting mixture again carefully and stir the resulting mixture 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 and dry with Na2SO4. Purify the crude product by flash chromatography (silica gel, EtOAc/CyH 1+7, later 1+5) to obtain 3′,4′,5′-Trimethoxy-biphenyl-2-carboxylic acid methyl ester (55) as a yellow solid (1.30 g, 99%). 1H NMR (400 MHz, CDCl3): 3.65 (s, 3H); 3.84 (s, 6H); 3.87 (s, 3H); 6.52 (s, 2H); 7.35-7.42 (m, 2H); 7.50 (t, 1H, J=8.0 Hz); 7.73 (d, 1H, J=8.0 Hz).

Workup

  1. custom(The following reaction
  2. customDegas the resulting mixture
  3. custom(5 times alternating vacuum and flushing with N2)
  4. customdegas the resulting mixture again carefully
  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. customPurify the crude product by flash chromatography (silica gel, EtOAc/CyH 1+7, later 1+5)

Sources & evidence

ORD record
ord-3e7b2fbe39aa46b983b7b4f7c8ccaa6c
Source dataset
uspto-grants-2011_04
Patent number
US07923473B2

Reaction notes

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