Pyridine → {[1-(3-[2-Naphthylmethoxy]phenyl)-4-phenylbutyl]oximino}acetic acid N-hydroxy-N-methyl-amide

HRID 1708494Notes

Reaction equation

HRID 1708494 reaction equation
C(Cl)(=O)C(Cl)=O.[CH:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][C:8]=1[CH2:17][O:18][C:19]1[CH:20]=[C:21]([CH:25]([O:35][N:36]=[CH:37][C:38]([OH:40])=O)[CH2:26][CH2:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:22]=[CH:23][CH:24]=1.C(N(CC)CC)C.Cl.[CH3:49][NH:50][OH:51].N1C=CC=CC=1>C(Cl)Cl.C(Cl)(Cl)Cl.C(OCC)(=O)C.CN(C=O)C>[OH:51][N:50]([CH3:49])[C:38](=[O:40])[CH:37]=[N:36][O:35][CH:25]([C:21]1[CH:22]=[CH:23][CH:24]=[C:19]([O:18][CH2:17][C:8]2[CH:9]=[CH:10][C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:7]=2)[CH:20]=1)[CH2:26][CH2:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

10

Reactant 5

HCID 1049PyridineHCID 8471Triethylamine2×HCID 65578Oxalyl chlorideHCID 77906N-methylhydroxylamine hydrochlorideHCID 54128871{[1-(3-[2-Naphthylmethoxy]-phenyl)4-phenylbutyl]oximino}acetic acid

Product 1

HCID 53757207{[1-(3-[2-Naphthylmethoxy]phenyl)-4-phenylbutyl]oximino}acetic acid N-hydroxy-N-methyl-amideYield 72.5%

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of DMF (0.5 mL) in methylene chloride (3 mL) at -30° to -20° C. was added oxalyl chloride (0.026 mL, 0.3 mmol) in methylene chloride (1 mL) dropwise. After 20 minutes, a solution of {[1-(3-[2-naphthylmethoxy]phenyl)-4-phenylbutyl]oximino}acetic acid (91 mg, 0.2 mmol) and triethylamine (0.03 mL, 0.2 mmol) in methylene chloride (5 mL) was added dropwise, and the mixture was stirred at -20° C. for 20 minutes. Then a solution of N-methylhydroxylamine hydrochloride (42 mg, 0.5 mmol), triethylamine (0.07 mL, 0.5 mmol) and pyridine (0.04 mL, 0.5 mmol) in chloroform (5 mL) was added. Upon completion of addition the mixture was allowed to warm to ambient temperature, stirred for 4 hours and then diluted with ethyl acetate (50 mL). The resulting mixture was washed with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was chromatographed on silica gel eluting with 1:1 methylene chloride-ethyl acetate to afford 70 mg of the title compound. 1H NMR (DMSO-d6, 300 MHz) δ 1.8 (m, 2H), 2.61 (t, J=7Hz, 2H), 2.77 (t, J=7Hz, 2H), 3.1 (s, 3H), 4.9 (s, 2H), 5.3 (s,2H), 7.2 (m, 9H), 7.53 (dd, J=6Hz, 4Hz, 2H), 7.6 (dd, J=8Hz, 2Hz, 1H), 7.96 (m, 4H), 9.9 (s,1H). IR (CDCl3): 3640, 3520, 3220, 1640,1600 cm-1. MS (DCI/NH3) m/e 483 (M+H)+, 500 (M+H+NH3)+. Analysis calcd for C30H30N2O4 ·0.5 H2O: C,73.30; H, 6.36; N, 5.70. Found: C, 73.24; H, 5.89; N. 5.39.

Workup

  1. additionUpon completion of addition the mixture
  2. temperatureto warm to ambient temperature
  3. stirringstirred for 4 hours
  4. washThe resulting mixture was washed with water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed on silica gel eluting with 1:1 methylene chloride-ethyl acetate

Sources & evidence

ORD record
ord-8741ad1d69594fd4861abfbeda8138b6
Source dataset
uspto-grants-1994_10
Patent number
US05358955

Reaction notes

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