2,4-Difluoroaniline → [2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(2-fluoro-5-hydroxy-phenyl)-methanone

HRID 1012655Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[C:14]([OH:16])[CH:13]=[CH:12][C:11]=2[F:17])=[O:9])=[C:4]([Cl:18])[CH:3]=1.[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[NH2:27].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[Cl:18][C:4]1[CH:3]=[C:2]([NH:27][C:21]2[CH:22]=[CH:23][C:24]([F:26])=[CH:25][C:20]=2[F:19])[CH:7]=[CH:6][C:5]=1[C:8]([C:10]1[CH:15]=[C:14]([OH:16])[CH:13]=[CH:12][C:11]=1[F:17])=[O:9]

Participants

Conditions

Temperature: 130 °C

Procedure

Compound 511 (200 mg, 0.6 mmol) was dissolved in dry 1,4-dioxane (5 mL) in a reaction vial under an argon atmosphere. 2,4-Difluoro-phenylamine (78 mg, 62 μL, 0.6 mmol) was added and dissolved in the solvent. Rac-BINAP (17 mg, 0.028 mmol), Pd2(dba)3 (17 mg, 0.018 mmol) and Cs2CO3 (277 mg, 0.85 mmol) were added. The reaction vial was flushed with argon, closed and then stirred at 130° C. for 40 min. In a microwave oven. The reaction mixture was allowed to cool to RT, filtered through Celite and then purified by continuous gradient flash chromatography using EtOAc/petroleum ether (40-60)(v:v=1:7 to 1:3) as the eluent to afford the title compound as a yellow solid.

Workup

dissolutiondissolved in the solvent
customThe reaction
customvial was flushed with argon
customclosed
temperatureto cool to RT
filtrationfiltered through Celite
custompurified by continuous gradient flash chromatography

Sources & evidence

ORD record: ord-f9dc97f4ae224e29868f362446c62f46
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977387B2

Reaction notes

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