Sodium Carbonate → HCID 86663044, compound

HRID 2410797Notes

Reaction equation

HRID 2410797 reaction equation
[CH:1]([O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10](B(O)O)=[CH:9][CH:8]=1)=[O:6])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].[NH2:22][C:23]1[C:32](Br)=[N:31][C:30]([Br:34])=[CH:29][C:24]=1[C:25]([O:27][CH3:28])=[O:26]>>[NH2:22][C:23]1[C:32]([C:10]2[CH:11]=[CH:12][C:7]([C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[O:6])=[CH:8][CH:9]=2)=[N:31][C:30]([Br:34])=[CH:29][C:24]=1[C:25]([O:27][CH3:28])=[O:26]

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 27347034-ISOPROPOXYCARBONYLPHENYLBORONIC ACIDHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

Product 1

HCID 86663044HCID 86663044, compoundYield 73%

Conditions

Temperature
110 °C

Procedure

A mixture of 4-isopropoxycarbonylphenylboronic acid (0.98 g, 4 7 mmol), sodium carbonate (1.02 g, 9.58 mmol), tetrakistriphenylphosphine palladium (0) (0.205 g, 0.177 mmol), and methyl 3-amino-2,6-dibromoisonicotinate (1.1 g, 3 6 mmol) in a vial was flushed with nitrogen. Toluene (12 mL) and methanol (4 mL) were added and the reaction stirred at 110° C. for 16 h. The reaction mixture was partitioned between EtOAc and sat. aq. sodium bicarbonate solution. The organic phase was washed with sat. aq. sodium bicarbonate solution, brine, and dried with sodium sulfate. Removal of the solvents followed by silica gel chromatography (step gradient elution with hexane containing 0 to 20% EtOAc afforded methyl 3-amino-6-bromo-2-(4-(isopropoxycarbonyl)phenyl)isonicotinate (1.04 g, 2.59 mmol, 73% yield). MS (ESI) m/z 393.00 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 8.14 (2H, d, J=8.24 Hz), 7.84 (1H, s), 7.69 (2H, d, J=8.24 Hz), 5.94 (2H, br. s.), 5.27 (1H, dt, J=12.51, 6.26 Hz), 3.93 (3H, s), 1.38 (6H, d, J=6.10 Hz).

Workup

  1. customwas flushed with nitrogen
  2. additionToluene (12 mL) and methanol (4 mL) were added
  3. customThe reaction mixture was partitioned between EtOAc and sat. aq. sodium bicarbonate solution
  4. washThe organic phase was washed with sat. aq. sodium bicarbonate solution, brine
  5. dry with materialdried with sodium sulfate
  6. customRemoval of the solvents
  7. washstep gradient elution with hexane containing 0 to 20% EtOAc

Sources & evidence

ORD record
ord-26bf30ad1ca942de9ccafb89db657ca5
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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