2-Amino-4-methylpyridine → N-(4-Methylpyridin-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

HRID 928306Notes

Reaction equation

HRID 928306 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:19][C:20]1([CH3:36])[C:24]([CH3:26])([CH3:25])[O:23][B:22]([C:27]2[CH:35]=[CH:34][C:30]([C:31](Cl)=[O:32])=[CH:29][CH:28]=2)[O:21]1>C1COCC1.ClCCl>[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:31](=[O:32])[C:30]2[CH:29]=[CH:28][C:27]([B:22]3[O:23][C:24]([CH3:25])([CH3:26])[C:20]([CH3:36])([CH3:19])[O:21]3)=[CH:35][CH:34]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 15332-Amino-4-methylpyridineHCID 2733832Lithium HexamethyldisilazideHCID 579816664-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl chloride

Product 1

HCID 17999246N-(4-Methylpyridin-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideYield 41.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 4-methylpyridin-2-amine (7.86 mmol, 850 mg) in THF (50 mL) was added dropwise a solution of 1M LiHMDS in THF (8.0 mmol, 8 mL) at room temperature. After the reaction mixture turned dark green, a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl chloride (9.6 mmol, 2.56 g) in dichloromethane (55 mL) was added dropwise. The mixture was stirred at room temperature for 2.5 h and was then concentrated. 3% aq. Citric acid solution (18 mL) was added and the mixture was extracted with dichloromethane (2×15 mL). The combined organic layer was washed with 3% aq. citric acid solution, dried over magnesium sulfate, filtered and evaporated. The residue was dissolved in THF (15 mL) and 6M NaOH solution (15 mL) was added. The mixture was stirred for 4 h. at room temperature. Ethyl acetate was added and the layers were separated. The organic layer was washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by chromatography on silica (eluent: DCM/MeOH=98/2 to DCM/MeOH=95/5) to yield 1.1 g of N-(4-methylpyridin-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (40.7%).

Workup

  1. concentrationwas then concentrated
  2. addition3% aq. Citric acid solution (18 mL) was added
  3. extractionthe mixture was extracted with dichloromethane (2×15 mL)
  4. washThe combined organic layer was washed with 3% aq. citric acid solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in THF (15 mL)
  9. addition6M NaOH solution (15 mL) was added
  10. stirringThe mixture was stirred for 4 h. at room temperature
  11. additionEthyl acetate was added
  12. customthe layers were separated
  13. washThe organic layer was washed with water and brine
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. customevaporated
  17. customThe residue was purified by chromatography on silica (eluent: DCM/MeOH=98/2 to DCM/MeOH=95/5)

Sources & evidence

ORD record
ord-32abf8f9aa4048838b2226160407b29d
Source dataset
uspto-grants-2016_03
Patent number
US09290504B2

Reaction notes

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