Sodium Carbonate → HCID 59337631, compound

HRID 12251Notes

Reaction equation

HRID 12251 reaction equation
[CH3:1][O:2][C:3](=[O:24])[C:4]1[C:9]([F:10])=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[C:6]([N+:20]([O-:22])=[O:21])[C:5]=1[NH2:23].[CH3:25][N:26]1[CH:31]=[CH:30][C:29](OS(C(F)(F)F)(=O)=O)=[CH:28][C:27]1=[O:40].[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[CH3:1][O:2][C:3](=[O:24])[C:4]1[C:9]([F:10])=[C:8]([C:29]2[CH:30]=[CH:31][N:26]([CH3:25])[C:27](=[O:40])[CH:28]=2)[CH:7]=[C:6]([N+:20]([O-:22])=[O:21])[C:5]=1[NH2:23]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 59337628Methyl 2-amino-6-fluoro-3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 59337641Trifluoro-methanesulfonic acid 1-methyl-2-oxo-1,2-dihydro-pyridin-4-yl ester

Product 1

HCID 59337631HCID 59337631, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 2-amino-5-bromo-6-fluoro-3-nitro-benzoic acid methyl ester (1.0 g, 3.4 mmol) in dioxane (25 mL), under nitrogen atmosphere, was added bispinacoladaboron (1.3 g, 5.1 mmol), dichloro[1,1′-bis(diphenylphosphine)ferrocene]palladium (II) dichlormethane adduct (0.125 g, 0.17 mmol), and potassium acetate (1.0 g, 10.2 mmol). The resulting mixture was heated at reflux for 18 hours, cooled to room temperature, diluted with ethyl acetate (50 ml) and filtered through Celite®. The resulting solid was triturated with hexanes (40 ml) three times to afford 0.515 g of 2-amino-6-fluoro-3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester. To a mixture of 2-amino-6-fluoro-3-nitro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester in ethylene glycol dimethyl ether (10 ml) was added trifluoro-methanesulfonic acid 1-methyl-2-oxo-1,2-dihydro-pyridin-4-yl ester (0.39 g, 1.5 mmol), lithium chloride (0.25 g, 6.0 mmol), sodium carbonate (1.1 ml, 2.2 mmol of 2M), and tetrakistriphenylphosphine palladium (0.18 g, 0.15 mmol). The resulting mixture was heated to 90° C. and allowed to stir for 18 hours. After cooling and concentration in vacuo, the residue was purified by chromatography (Silica Gel 0.5% methanol/dichloromethane to 2% methanol/dichloromethane) to provide the title compound (0.275 g, 25%). 1H NMR (500 MHz, CDCl3) δ 3.58 (s, 3H), 4.03 (s, 3H), 6.30 (d, 1H), 7.32 (d, 1H), 8.45 (br s, 2H), 8.53 (d, 1H)

Workup

  1. temperatureAfter cooling
  2. concentrationconcentration in vacuo
  3. customthe residue was purified by chromatography (Silica Gel 0.5% methanol/dichloromethane to 2% methanol/dichloromethane)

Sources & evidence

ORD record
ord-8f1b7bacbef04f158bc05613acb1e601
Source dataset
uspto-grants-2010_06
Patent number
US07727992B2

Reaction notes

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