Sodium Carbonate → tert-Butyl-4-(2-(5-(2-Chloropheny)-4-chloro-2-methoxyphenylamino)acetyl)piperazine-1-carboxylate

HRID 588778Notes

Reaction equation

[Cl:1][C:2]1[C:7](I)=[CH:6][C:5]([NH:9][CH2:10][C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)=[O:12])=[C:4]([O:26][CH3:27])[CH:3]=1.[Cl:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:22]([O:21][C:19]([N:16]1[CH2:17][CH2:18][N:13]([C:11](=[O:12])[CH2:10][NH:9][C:5]2[CH:6]=[C:7]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=3[Cl:28])[C:2]([Cl:1])=[CH:3][C:4]=2[O:26][CH3:27])[CH2:14][CH2:15]1)=[O:20])([CH3:25])([CH3:24])[CH3:23]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of tert-butyl 4-(2-(4-chloro-5-iodo-2-methoxyphenylamino)acetyl)piperazine-1-carboxylate (200 mg, 0.4 mmol) and 2-chlorophenylboronic acid (69 mg, 0.44 mmol) in 1,4-dioxane (10 mL) and water (2 mL), Pd(PPh3)4 (40 mg, 0.035 mmol) and Na2CO3 (212 mg, 2 mmol) were added. The mixture was stirred at 80° C. for 16 h. The mixture was allowed to cool to room temperature and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=4:1) to afford the desire product (150 mg, 76% yield).

Workup

temperatureto cool to room temperature
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=4:1)

Sources & evidence

ORD record: ord-8b8eddceec254772b6f520eaa97cb906
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227978B2

Reaction notes

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