Sodium Hydroxide → Methyl 4-(5-bromo-6-methoxypyridin-3-yl)-3,5-dimethylbenzoate

HRID 531247Notes

Reaction equation

HRID 531247 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[C:18]([CH3:19])=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=2[CH3:20])=[CH:5][CH:4]=1.C([O-])(=O)C.[K+].[Br:26]Br.[OH-].[Na+]>C(O)(=O)C.C(OCC)(=O)C>[Br:26][C:4]1[CH:5]=[C:6]([C:9]2[C:18]([CH3:19])=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=2[CH3:20])[CH:7]=[N:8][C:3]=1[O:2][CH3:1]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24408BromineHCID 517044Potassium AcetateHCID 90009124Methyl 4-(6-methoxypyridin-3-yl)-3,5-dimethylbenzoate

Product 1

HCID 90009097Methyl 4-(5-bromo-6-methoxypyridin-3-yl)-3,5-dimethylbenzoate

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Methyl 4-(6-methoxypyridin-3-yl)-3,5-dimethylbenzoate (Step B, 1.31 g, 4.83 mmol) and potassium acetate (2.369 g, 24.14 mmol) were dissolved in acetic acid (24 mL). Bromine (0.622 mL, 12.07 mmol) was added and the reaction was stirred at 80° C. The reaction was monitored by LCMS. Once complete, it was cooled to room temperature, diluted with ethyl acetate and added to a separatory funnel. Aqueous sodium hydroxide was added to neutralize the reaction. The reaction was partitioned between water and ethyl acetate, and the aqueous was extracted a second time with ethyl acetate. The combined organics were washed with brine, then dried over sodium sulfate, filtered and evaporated. The crude isolate was purified by silica gel chromatography, eluting with 2 column volumes of 4% Ethyl acetate in hexanes, followed by a gradient of 4-10% ethyl acetate/hexanes over 6 column volumes, followed by a gradient of 10-20% ethyl acetate/hexanes over 5 column volumes to give the title compound. 1H NMR (CDCl3, 500 MHz) δ7.88 (d, 1H), 67.79 (s, 2H), 67.63 (d, 1H), 64.07 (s, 3H), 63.93 (s, 3H), 62.11 (s, 6H).

Workup

  1. temperatureOnce complete, it was cooled to room temperature
  2. additionadded to a separatory funnel
  3. customthe reaction
  4. customThe reaction was partitioned between water and ethyl acetate
  5. extractionthe aqueous was extracted a second time with ethyl acetate
  6. washThe combined organics were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude isolate
  11. customwas purified by silica gel chromatography
  12. washeluting with 2 column volumes of 4% Ethyl acetate in hexanes

Sources & evidence

ORD record
ord-2590f9b8248040b78de1715aa6214fc0
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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