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

HRID 2261772Notes

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

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 mixture is stirred at 80° C. under N2 overnight. The reaction mixture is filtered through a Celite® pad eluting with EtOAc. The combined filtrate is concentrated under reduced pressure and the residue is purified by column chromatography (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

customis bubbled N2 for 15 minutes
filtrationThe reaction mixture is filtered through a Celite® pad
washeluting with EtOAc
concentrationThe combined filtrate is concentrated under reduced pressure
customthe residue is purified by column chromatography (0-15% EtOAc in hexanes)

Sources & evidence

ORD record: ord-90d83e49611948d8b1aa11a0de31b246
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07846960B2

Reaction notes

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