Sodium Carbonate → HCID 86663031, compound

HRID 2410778Notes

Reaction equation

HRID 2410778 reaction equation
[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[NH2:12][C:13]1[C:22](Br)=[N:21][C:20]([Br:24])=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16].C(=O)([O-])[O-].[Na+].[Na+]>>[NH2:12][C:13]1[C:22]([C:6]2[CH:7]=[CH:8][C:3]([CH2:2][OH:1])=[CH:4][CH:5]=2)=[N:21][C:20]([Br:24])=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16]

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

Product 1

HCID 86663031HCID 86663031, compoundYield 46%

Procedure

A mixture of 4-(hydroxymethyl)phenylboronic acid (2.35 g, 15.5 mmol), methyl 3-amino-2,6-dibromoisonicotinate (4.0 g, 12.9 mmol), tetrakistriphenylphosphine palladium(0) (0.895 g, 0.774 mmol), sodium carbonate (3.28 g, 31.0 mmol) was flushed with nitrogen and toluene (32.3 mL), and MeOH (10.75 mL) were added. The reaction was heated at reflux under nitrogen for 24 hr. It was partitioned between EtOAc and water. The organic phase was washed with brine, dried with sodium sulfate, and the solvents removed. The organic phase was washed with brine, dried with sodium sulfate and the solvent removed. The residue was chromatographed (step gradient elution with DCM containing 0 to 20% EtOAc afforded methyl 3-amino-6-bromo-2-(4-(hydroxymethyl)phenyl)isonicotinate (1.99 g, 5.90 mmol, 46% yield) as a yellow fluffy solid. MS (ESI) m/z 336.8 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 7.80 (1H, s), 7.61 (2H, d, J=8.24 Hz), 7.48 (2H, d, J=7.93 Hz), 5.94 (2H, br. s.), 4.75 (2H, d, J=5.80 Hz), 3.92 (3H, s), 1.72 (1H, t, J=5.80 Hz).

Workup

  1. customwas flushed with nitrogen and toluene (32.3 mL), and MeOH (10.75 mL)
  2. additionwere added
  3. temperatureThe reaction was heated
  4. temperatureat reflux under nitrogen for 24 hr
  5. customIt was partitioned between EtOAc and water
  6. washThe organic phase was washed with brine
  7. dry with materialdried with sodium sulfate
  8. customthe solvents removed
  9. washThe organic phase was washed with brine
  10. dry with materialdried with sodium sulfate
  11. customthe solvent removed
  12. customThe residue was chromatographed (
  13. washstep gradient elution with DCM containing 0 to 20% EtOAc

Sources & evidence

ORD record
ord-eeeef98e996a452398d64b4961eb4f53
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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