Pyridine → HCID 59016052, compound

HRID 968857Notes

Reaction equation

HRID 968857 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]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:47][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:46]=[CH:47][C:48]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:49][CH:50]=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 1049Pyridine2×HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 23584129HCID 23584129, compoundHCID 87622518HCID 87622518, compound

Product 1

HCID 59016052HCID 59016052, compoundYield 68.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

4-[4-(1-Ethoxycarbonyl-1-methyl-ethoxy)-phenyl] butyric acid (0.89 g, 3.02 mmol) was dissolved in ethyl acetate (10 mL). Oxalyl chloride (316 μL, 3.62 mmol) was added to this solution dropwise in the presence of a catalytic amount of N,N-dimethylformamide (17 μL, 0.24 mmol). Completion of acid chloride formation was verified by HPLC. The solution was then concentrated to remove excess oxalyl chloride and then redissolved in ethyl acetate (7 mL). This solution was then added dropwise to a suspension of N-Methyl-1-(4-t-butylphenylmethyl)hydrazine carboxamide methanesulfonate (1.02 g, 3.07 mmol) and pyridine (256 μL, 6.14 mmol) in ethyl acetate (10 mL) at 0° C. After stirring at 0° C. for 3 h, an additional charge of pyridine (256 μL, 6.14 mmol) was added and the solution was stirred at 0° C. for 1 h. The solution was warmed to rt and washed with 1N HCl (2×10 mL) and then with 5% aq. NaHCO3 (2×10 mL). The organic layer was dried (MgSO4), filtered and concentrated to an orange oil. Column chromatography (SiO2, ethyl acetate) afforded the title compound as a clear oil (1.06 g, 68%): 1H NMR (DMSO-d6, 60° C.) δ 9.50 (s, 1H), 7.29 (d, 2H, J=8 Hz), 7.16 (d, 2H, J=8 Hz), 7.01 (d, 2H, J=8 Hz), 6.71 (d, 2H, J=8 Hz), 6.27 (br s, 1H), 4.52 (br s, 2H), 4.15 (q, J=7 Hz), 2.58 (d, 3H, J=4 Hz), 2.44 (t, 2H, J=7 Hz ), 2.07 (t, 2H, J=7 Hz ), 1.72 (quint, 2H, J=7 Hz), 1.48 (s, 6H), 1.25 (s, 9H), (1.17 (t, 3H, J=7 Hz); 13C NMR (DMSO-d6) δ 174.0, 172.0, 158.7, 153.8, 149.9, 135.9, 129.7, 128.7, 125.6, 119.5, 79.2, 61.6, 50.8, 34.8, 34.4, 33.4, 31.8, 27.7, 27.1, 25.7, 14.6.; IR (CHCl3) 3009, 2966, 1671, 1509, 1211 cm−1; Anal. Calcd. for C29H41N3O5: C, 68.08; H, 8.08; N, 8.21. Found:,C, 67.70; H, 7.86; N, 8.11.

Workup

  1. concentrationThe solution was then concentrated
  2. customto remove excess oxalyl chloride
  3. dissolutionredissolved in ethyl acetate (7 mL)
  4. additionwas added
  5. stirringthe solution was stirred at 0° C. for 1 h
  6. temperatureThe solution was warmed to rt
  7. washwashed with 1N HCl (2×10 mL)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated to an orange oil

Sources & evidence

ORD record
ord-d4c3f149d08d43b5ac66d8c67559b192
Source dataset
uspto-grants-2007_12
Patent number
US07304062B2

Reaction notes

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