Phenylacetaldehyde → N-benzyl-2-(3-benzylisoxazol-5-yl)-4-methylthiazole-5-carboxamide

HRID 2381862Notes

Reaction equation

HRID 2381862 reaction equation
[C:1]1([CH2:7][CH:8]=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[NH2:11][OH:12].[OH-].[Na+].CC1C=CC(S(NCl)(=O)=O)=CC=1.[CH2:27]([NH:34][C:35]([C:37]1[S:41][C:40]([C:42]#[CH:43])=[N:39][C:38]=1[CH3:44])=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(O)(C)(C)C.O.[Cu]I>[CH2:27]([NH:34][C:35]([C:37]1[S:41][C:40]([C:42]2[O:12][N:11]=[C:8]([CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:43]=2)=[N:39][C:38]=1[CH3:44])=[O:36])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

9

Reactant 5

HCID 998PhenylacetaldehydeHCID 14798Sodium HydroxideHCID 31388TosylchloramideHCID 443297Hydroxyamine hydrochlorideHCID 73213266N-benzyl-2-ethynyl-4-methylthiazole-5-carboxamide

Product 1

HCID 24960062N-benzyl-2-(3-benzylisoxazol-5-yl)-4-methylthiazole-5-carboxamideYield 53%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Procedure

To a solution of 2-phenylacetaldehyde (0.05 mL, 0.44 mmol) in t-butanol (2.5 mL) and water (2.5 mL) was added hydroxylamine hydrochloride (0.03 g, 0.45 mmol) and sodium hydroxide (0.02 g, 0.50 mmol). The reaction mixture was stirred at ambient temperature for 3 hours, followed by the addition of chloramine T (0.14 g, 0.50 mmol), N-benzyl-2-ethynyl-4-methylthiazole-5-carboxamide (0.10 g, 0.39 mmol) and copper(I) iodide (0.01 g, 0.06 mmol). The reaction mixture was stirred for 18 hours at ambient temperature and extracted with ethyl acetate, washed with 10% ammonium chloride solution and brine. The organic solution was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography to afford the title compound as a white solid (0.08 g, 53%): mp 103-104° C.; 1H NMR (300 MHz, CDCl3) δ 7.36-7.17 (m, 10H), 6.60 (s, 1H), 6.55 (t, J=5.6 Hz, 1H), 4.56 (d, J=5.6 Hz, 2H), 4.01 (s, 2H), 2.67 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.2, 163.2, 161.1, 156.8, 152.8, 137.5, 136.5, 128.9, 128.8, 127.8, 127.2, 103.1, 44.3, 32.3, 17.3; MS (ES+) m/z 390.3 (M+1).

Workup

  1. stirringThe reaction mixture was stirred for 18 hours at ambient temperature
  2. extractionextracted with ethyl acetate
  3. washwashed with 10% ammonium chloride solution and brine
  4. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-5794c6b27a964f2db1028a679efcd335
Source dataset
uspto-grants-2012_09
Patent number
US08258160B2

Reaction notes

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