Pyridine → HCID 59016005, compound

HRID 968854Notes

Reaction equation

HRID 968854 reaction equation
[CH2:1]([O:3][C:4]([C:6]([CH3:21])([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][C:18]([OH:20])=O)=[CH:11][CH:10]=1)[CH3:7])=[O:5])[CH3:2].C(Cl)(=O)C(Cl)=O.CN(C)C=O.CS(O)(=O)=O.[CH3:38][NH:39][C:40]([N:42]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[C:47]([CH3:52])[CH:46]=1)[NH2:43])=[O:41].N1C=CC=CC=1>C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]([CH3:7])([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][CH2:17][C:18]([NH:43][N:42]([CH2:44][C:45]2[CH:50]=[CH:49][C:48]([CH3:51])=[C:47]([CH3:52])[CH:46]=2)[C:40]([NH:39][CH3:38])=[O:41])=[O:20])=[CH:13][CH:14]=1)[CH3:21])=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 23584129HCID 23584129, compoundHCID 86628491HCID 86628491, compound

Product 1

HCID 59016005HCID 59016005, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

4-[4-(1-Ethoxycarbonyl-1-methyl-ethoxy)-phenyl] butyric acid (1.46 g, 4.96 mmol) was dissolved in ethyl acetate (10 mL). Oxalyl chloride (474 μL, 5.46 mmol) was added to this solution dropwise in the presence of a catalytic amount of N,N-dimethylformamide (30.6 μL, 0.39 mmol). Completion of acid chloride formation was verified by HPLC. This solution was then added dropwise to a suspension of N-Methyl-1-(3,4-dimethylphenylmethyl)hydrazine carboxamide methanesulfonate (1.50 g, 4.95 mmol) and pyridine (1.00 μL, 12.9 mmol) in ethyl acetate (15 mL) at 0° C. After stirring at 0° C. for 6 h, the solution was warmed to rt and washed with 1N HCl (2×20 mL), 5% aq. NaHCO3 (2×20 mL) and sat'd aq. NaCl. The organic layer was dried (MgSO4), filtered and concentrated to a yellow oil. The oil was purified by column chromatography (SiO2, 9:1 ethyl acetate:hexanes), to afford the title compound as a clear oil (1.48 g, 62%): 1H NMR (DMSO-d6, 60° C.) δ 9.42 (s, 1H), 6.97 (m, 5H), 6.71 (d, 2H, J=8 Hz), 6.23 (s, 1H), 4.46 (s, 2H), 4.15 (q, J=7 Hz), 2.59 (s, 3H), 2.43 (t, 2H, J=8 Hz ), 2.15 (s, 6H), 2.06 (t, 2H, J=8 Hz ), 1.70 (quint, 2H, J=7 Hz), 1.48 (s, 6H), 1.17 (t, 3H, J=7 Hz); 13C NMR (DMSO-d6) δ 174.0, 172.0, 158.7, 153.8, 136.4, 136.0, 135.9, 135.4, 130.2, 129.9, 129.7, 126.5, 119.5, 79.2, 61.6, 50.6, 34.4, 33.5, 27.6, 27.2, 25.7, 20.0, 19.7, 14.6; IR (CHCl3) 3009, 1669, 1509, 1142 cm−1; Exact Mass Calcd. for C27H38N3O5: 484.2811. Found: 484.2822.

Workup

  1. temperaturethe solution was warmed to rt
  2. washwashed with 1N HCl (2×20 mL), 5% aq. NaHCO3 (2×20 mL)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated to a yellow oil
  6. customThe oil was purified by column chromatography (SiO2, 9:1 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-4a6eb5517da3436ab914fd8557f52939
Source dataset
uspto-grants-2007_12
Patent number
US07304062B2

Reaction notes

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