Sodium Carbonate → Glycine, N-(2',5',6-trichloro-4-methoxy[1,1'-biphenyl]-3-yl)-

HRID 588818Notes

Reaction equation

HRID 588818 reaction equation
[Cl:1][C:2]1[C:7](I)=[CH:6][C:5]([NH:9][CH2:10][C:11]([O:13]C)=[O:12])=[C:4]([O:15][CH3:16])[CH:3]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=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>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[C:7]1[C:2]([Cl:1])=[CH:3][C:4]([O:15][CH3:16])=[C:5]([NH:9][CH2:10][C:11]([OH:13])=[O:12])[CH:6]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27733712,5-Dichlorobenzeneboronic acidHCID 117610930Glycine, N-(4-chloro-5-iodo-2-methoxyphenyl)-, methyl ester

Product 1

HCID 90455762Glycine, N-(2',5',6-trichloro-4-methoxy[1,1'-biphenyl]-3-yl)-Yield 59.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 2-(4-chloro-5-iodo-2-methoxyphenylamino)acetate (5.0 g, 14.08 mmol), 2,5-dichlorophenylboronic acid (4.03 g, 21.12 mmol), Pd(PPh3)4 (1.626 g, 1.04 mmol), Na2CO3 (4.477 g, 42.24 mmol) in 1,4-dioxane (100 mL) and water (20 mL) was stirred at reflux under argon for 6 h. Then reaction mixture was allowed to cool to room temperature, quenched with water and acidified with HCl (10% in water) to adjust the pH to 3-4. The mixture was extracted with ethyl acetate, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (50% petroleum ether/ethyl acetate) to afford the desired product (3 g, 59% yield) as an off-white solid. ESI-MS m/z: 360.2 [M−H]−.

Workup

  1. temperatureat reflux under argon for 6 h
  2. customThen reaction mixture
  3. customquenched with water
  4. extractionThe mixture was extracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel (50% petroleum ether/ethyl acetate)

Sources & evidence

ORD record
ord-411d237898d04fad906bc1d5294e1652
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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