O-Methylhydroxylamine → 1-[(2'-Methoxyaminocarbonylbiphenyl-4-yl)methyl]-2-butyl-4-chloro-5-(2-methoxyethoxymethoxymethyl)imidazole

HRID 465816Notes

Reaction equation

HRID 465816 reaction equation
C(Cl)(=O)C(Cl)=O.CN1CCOCC1.[C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:30]2[C:34]([CH2:35][O:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH3:42])=[C:33]([Cl:43])[N:32]=[C:31]2[CH2:44][CH2:45][CH2:46][CH3:47])=[CH:25][CH:24]=1)(O)=[O:15].[O:48]([NH2:50])[CH3:49]>C(Cl)(Cl)Cl.C(OCC)(=O)C.CN(C)C=O>[CH3:49][O:48][NH:50][C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]1[CH:24]=[CH:25][C:26]([CH2:29][N:30]2[C:34]([CH2:35][O:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH3:42])=[C:33]([Cl:43])[N:32]=[C:31]2[CH2:44][CH2:45][CH2:46][CH3:47])=[CH:27][CH:28]=1)=[O:15]

Participants

8

Reactant 4

HCID 4113O-MethylhydroxylamineHCID 79724-Methylmorpholine2×HCID 65578Oxalyl chlorideHCID 156980891-[(2'-Carboxybiphenyl-4-yl)methyl]-2-butyl-4-chloro-5-(2-methoxyethoxymethoxymethyl)imidazole

Product 1

HCID 156980901-[(2'-Methoxyaminocarbonylbiphenyl-4-yl)methyl]-2-butyl-4-chloro-5-(2-methoxyethoxymethoxymethyl)imidazole

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 0.24 ml of oxalyl chloride in 5 mL of chloroform was added dropwise to a solution of 1 mL of dimethylformamide in 4 mL of chloroform at -20°. After this solution had been stirred at -20° for 20 minutes, 0.28 mL of N-methylmorpholine was added followed by 1.21 g of 1-[(2'-carboxybiphenyl-4-yl)-methyl]-2-butyl-4-chloro-5-(2-methoxyethoxymethoxymethyl)imidazole. After another 20 minutes at -20°, 0.55 ml of N-methylmorpholine and 1.35 mL of methoxylamine were added to the mixture. The reaction mixture was warmed slowly to 25°, stirred at 25° for 4 hours, and finally refluxed for 40 hours. After cooling the mixture was diluted with ethyl acetate. The resulting solution was washed with 10% hydrochloric acid, water, 10% sodium bicarbonate solution and brine. Finally the solution was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Column chromatography (elution: methanol/chloroform) furnished 0.21 g of 1-[(2'-methoxyaminocarbonylbiphenyl-4-yl)methyl]-2-butyl-4-chloro-5-(2-methoxyethoxymethoxymethyl)imidazole. NMR (200 MHz, CDCl3) δ7.85 (s, 1H); 7.63 (d, 1H); 7.53-7.33 (m, 5H); 7.05 (d, 2H); 5.20 (s, 2H); 4.67 (s, 2H); 4.47 (s, 2H); 3.63 (m, 5H); 3.55 (m, 2H); 3.36 (s, 3H); 2.56 (t, 2H); 1.67 (m, 2H); 1.32 (m, 2H); 0.87 (t, 3H).

Workup

  1. waitAfter another 20 minutes at -20°
  2. temperatureThe reaction mixture was warmed slowly to 25°
  3. stirringstirred at 25° for 4 hours
  4. temperaturefinally refluxed for 40 hours
  5. temperatureAfter cooling the mixture
  6. washThe resulting solution was washed with 10% hydrochloric acid, water, 10% sodium bicarbonate solution and brine
  7. dry with materialFinally the solution was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. washColumn chromatography (elution: methanol/chloroform)

Sources & evidence

ORD record
ord-0b1aecd4dbd540ea968e5ade55938121
Source dataset
uspto-grants-1992_10
Patent number
US05153197

Reaction notes

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