4-Chloro-2-toluidine → [2-Chloro-4-(4-chloro-2-methyl-phenylamino)-phenyl]-(2-fluoro-5-hydroxy-phenyl)-methanone

HRID 1012659Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([CH3:9])[CH:3]=1.Br[C:11]1[CH:16]=[CH:15][C:14]([C:17]([C:19]2[CH:24]=[C:23]([OH:25])[CH:22]=[CH:21][C:20]=2[F:26])=[O:18])=[C:13]([Cl:27])[CH:12]=1.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:27][C:13]1[CH:12]=[C:11]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[CH3:9])[CH:16]=[CH:15][C:14]=1[C:17]([C:19]1[CH:24]=[C:23]([OH:25])[CH:22]=[CH:21][C:20]=1[F:26])=[O:18]

Participants

Conditions

Temperature: 130 °C

Procedure

4-Chloro-2-methyl-phenylamine (73 μL, 0.60 mmol) was dissolved in 5 mL dry 1,4-dioxane in a reaction vial under an argon atmosphere. Compound 511 (200 mg, 0.60 mmol) was added and dissolved in the solvent. Rac-BINAP (18 mg, 0.028 mmol), Pd2(dba)3 (17 mg, 0.018 mmol) and Cs2CO3 (277 mg, 0.84 mmol) were added. The reaction vial was flushed with argon, closed and then stirred at 130° C. for 10 min. in a microwave oven. The reaction mixture was filtered through Celite and then purified by continuous gradient flash chromatography using EtOAc/petroleum ether (40-60) (v:v=1:9 to 1:4) as the eluent to afford the title compound as yellow solid. 13C NMR (CDCl3)

Workup

dissolutiondissolved in the solvent
customThe reaction
customvial was flushed with argon
customclosed
filtrationThe reaction mixture was filtered through Celite
custompurified by continuous gradient flash chromatography

Sources & evidence

ORD record: ord-9dc428c37975492183a6545d9433f74a
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977387B2

Reaction notes

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