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

HRID 705104Notes

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 stirring solution of 5-iodo-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide (1.0 g, 1 eq) 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) at room temperature, and the reaction mixture was heated under microwave irridiation at 150° C. for one hour. The reaction mixture was diluted with EtOAc, and the organic layer was separated, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with hexane-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

customthe organic layer was separated
washwashed with water and brine
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel with hexane-ethyl acetate (8:1 to 2:1)

Sources & evidence

ORD record: ord-8988d556dff44ca9aad84fc036dd39b1
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09173861B2

Reaction notes

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