Potassium Phosphate, Tribasic → 4'-amino-5'-fluoro-N,2'-dimethylbiphenyl-4-carboxamide

HRID 2091941Notes

Reaction equation

Br[C:2]1[C:8]([CH3:9])=[CH:7][C:5]([NH2:6])=[C:4]([F:10])[CH:3]=1.[CH3:11][NH:12][C:13]([C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1)=[O:14].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(O)CCC.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]>[NH2:6][C:5]1[C:4]([F:10])=[CH:3][C:2]([C:18]2[CH:19]=[CH:20][C:15]([C:13]([NH:12][CH3:11])=[O:14])=[CH:16][CH:17]=2)=[C:8]([CH3:9])[CH:7]=1

Participants

Conditions

Temperature: 130 °C

Procedure

The mixture of 4-bromo-2-fluoro-5-methylaniline (203 mg, 1.0 mmol), 4-(methylcarbamoyl)phenylboronic acid (179 mg, 1.0 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (82 mg, 0.2 mmol), Pd2(dba)3 (91 mg, 0.1 mmol), and K3PO4 (424 mg, 2.0 mmol) in 5.0 mL of n-butanol is degassed and heated at 130° C. for 1 h. The reaction mixture is concentrated in vacuo. The crude product mixture is partitioned between EtOAc and brine, the collected organic extracts are dried (Na2SO4), concentrated and purified with silica gel chromatography (EtOAc/hexanes:1/4) to afford 4′-amino-5′-fluoro-N,2′-dimethylbiphenyl-4-carboxamide; ESMS m/z 259.1 (M+H+).

Workup

customis degassed
concentrationThe reaction mixture is concentrated in vacuo
customThe crude product mixture is partitioned between EtOAc and brine
dry with materialthe collected organic extracts are dried (Na2SO4)
concentrationconcentrated
custompurified with silica gel chromatography (EtOAc/hexanes:1/4)

Sources & evidence

ORD record: ord-ba6ef84374bc4dd28b105bee3e829d0c
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440681B2

Reaction notes

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