Potassium Carbonate → 5-(4-Methoxy-2-methyl-phenyl)-4-methyl-thiophene-2-carboxylic acid methyl ester

HRID 424792Notes

Reaction equation

HRID 424792 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[C:5]([CH3:12])[CH:4]=1.[CH3:13][O:14][C:15]([C:17]1[S:18][C:19](Br)=[C:20]([CH3:22])[CH:21]=1)=[O:16].C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=2[CH3:12])=[C:20]([CH3:22])[CH:21]=1)=[O:16]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2773486(4-Methoxy-2-methylphenyl)boronic acidHCID 2795489Methyl 5-bromo-4-methylthiophene-2-carboxylate

Product 1

HCID 667042235-(4-Methoxy-2-methyl-phenyl)-4-methyl-thiophene-2-carboxylic acid methyl esterYield 39.1%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 4-methoxy-2-methylphenylboronic acid (912 mg, 6 mmol), 5-bromo-4-methyl-thiophene-2-carboxylic acid methyl ester (1.1 g, 5 mmol) and K2CO3 (1.38 g, 10 mmol) in toluene (30 mL) and water (5 mL) is bubbled N2 for 15 minutes followed by addition of tetrakis(triphenylphosphine) palladium (289 mg, 0.25 mmol). The reaction mixture is stirred at 80° C. under N2 overnight. The reaction mixture is filtered through a diatomaceous earth pad eluting with EtOAc. The combined filtrate is concentrated and the residue is purified by column chromatography on silica gel eluting with 0-15% EtOAc in hexanes to give 5-(4-methoxy-2-methyl-phenyl)-4-methyl-thiophene-2-carboxylic acid methyl ester (540 mg, 39%). 1H NMR (CDCl3): δ 7.63 (s, 1H), 7.15 (d, 1H, J=8.4 Hz), 6.82 (d, 1H, J=2.8 Hz), 6.78 (dd, 1H, J=2.8, J=8.4 Hz), 4.79 (bs, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 2.17 (s, 3H), 2.02 (s, 3H).

Workup

  1. customis bubbled N2 for 15 minutes
  2. filtrationThe reaction mixture is filtered through a diatomaceous earth pad
  3. washeluting with EtOAc
  4. concentrationThe combined filtrate is concentrated
  5. customthe residue is purified by column chromatography on silica gel eluting with 0-15% EtOAc in hexanes

Sources & evidence

ORD record
ord-2f2beeb32f9641ea98cfa1f7a9d1f493
Source dataset
uspto-grants-2012_01
Patent number
US08106077B2

Reaction notes

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