Acetic Anhydride → 5-Acetyl-4'-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide

HRID 1888917Notes

Reaction equation

[CH3:1][O:2][CH2:3][CH:4]([NH:6][C:7]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[CH:12]=[C:13](I)[CH:14]=1)=[O:8])[CH3:5].[Li+].[Cl-].CCN(C(C)C)C(C)C.[C:34](OC(=O)C)(=[O:36])[CH3:35]>CN(C=O)C.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][CH2:3][CH:4]([NH:6][C:7]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[CH:12]=[C:13]([C:34](=[O:36])[CH3:35])[CH:14]=1)=[O:8])[CH3:5]

Participants

Conditions

Temperature: 150 °C

Procedure

To a stirred, room temperature solution of 5-iodo-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide (1.0 g, 2.4 mmol)) in 3 ml anhydrous DMF were added LiCl (520 mg, 5 eq), Pd2(dba)3 (18.34 mg, 1.3% eq), DIPEA (0.8545 ml, 2 eq) and acetic anhydride (1.1636 ml, 5 eq). The reaction mixture was heated by microwave irridiation to 150° C. for 1 hour, then cooled and diluted with EtOAc. The combined organic layers were washed with water, brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with hexanes-ethyl acetate 8:1 to 2:1), giving 5-acetyl-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide (538 mg, 75%). MS (M+H)=326.

Workup

temperaturecooled
washThe combined organic layers were washed with water, brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel with hexanes-ethyl acetate 8:1 to 2:1),

Sources & evidence

ORD record: ord-e6d9b4be936146b5bc1ffc66bf2e9d16
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501933B2

Reaction notes

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