Iodine → N-benzyl-2-(2-benzyloxazol-5-yl)-4-methylthiazole-5-carboxamide

HRID 2381871Notes

Reaction equation

HRID 2381871 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([C:16]2[O:20][CH:19]=[N:18][CH:17]=2)=[N:13][C:12]=1[CH3:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.II.[Br-].[CH2:30]([Zn+])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([C:16]2[O:20][C:19]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[N:18][CH:17]=2)=[N:13][C:12]=1[CH3:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 807IodineHCID 25517Ammonium ChlorideHCID 24960064N-benzyl-4-methyl-2-(oxazol-5-yl)thiazole-5-carboxamideHCID 178418339ButyllithiumHCID 178419772HCID 178419772, compound

Product 1

HCID 24960065N-benzyl-2-(2-benzyloxazol-5-yl)-4-methylthiazole-5-carboxamideYield 5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-benzyl-4-methyl-2-(oxazol-5-yl)thiazole-5-carboxamide (0.20 g, 0.67 mmol) in tetrahydrofuran (20 mL) was added n-butyllithium (0.88 mL of 1.6 M solution in hexanes, 1.40 mmol) at −78° C. The reaction mixture was stirred for 30 minutes, and iodine (0.17 g, 0.67 mmol) was added. The reaction was slowly warmed to ambient temperature over 4 hours and stirred for another 18 hours. Tetrakis-(triphenylphosphine)palladium (0.04 g, 0.03 mmol) and benzylzinc bromide (2.5 mL of 0.5 M solution in tetrahydrofuran, 1.25 mmol) were added. The reaction mixture was heated to 50° C. for 17 hours, cooled to ambient temperature, added saturated ammonium chloride solution (10 mL) to quench the reaction. The mixture was extracted with ethyl acetate. The organic solution was washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography to afford the title compound in 5% yield (0.02 g): mp 141-142° C.; 1H NMR (300 MHz, CDCl3) δ 7.82 (s, 1H), 7.44-7.15 (m, 10H), 6.07 (t, J=5.6 Hz, 1H), 4.61 (d, J=5.6 Hz, 2H), 4.34 (s, 2H), 2.74 (s, 3H); MS (ES+) m/z 390.2 (M+1).

Workup

  1. stirringstirred for another 18 hours
  2. temperatureThe reaction mixture was heated to 50° C. for 17 hours
  3. temperaturecooled to ambient temperature
  4. customto quench
  5. customthe reaction
  6. extractionThe mixture was extracted with ethyl acetate
  7. washThe organic solution was washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-4aab40b0b0e84af081268d94a9b50e88
Source dataset
uspto-grants-2012_09
Patent number
US08258160B2

Reaction notes

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