Toluene → HCID 49820124, compound

HRID 391293Notes

Reaction equation

HRID 391293 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][C:10]=2[O:17][CH3:18])[CH:6]=[N:7][CH:8]=1)=O.[CH2:19]([S:21]([NH2:24])(=[O:23])=[O:22])[CH3:20].[NH4+].[Cl-].[C:27]1([CH3:33])C=CC=C[CH:28]=1>C(OCC)(=O)C.[Cl-].[Na+].O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:13]([C:12]1[CH:15]=[CH:16][C:9]([C:5]2[CH:4]=[C:3]([CH:1]([CH:33]3[CH2:27][CH2:28]3)[NH:24][S:21]([CH2:19][CH3:20])(=[O:23])=[O:22])[CH:8]=[N:7][CH:6]=2)=[C:10]([O:17][CH3:18])[CH:11]=1)#[N:14]

Participants

8

Reactant 4

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 73702EthanesulfonamideHCID 595784304-(5-Formyl-pyridin-3-yl)-3-methoxy-benzonitrile

Product 1

HCID 49820124HCID 49820124, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-36 °C

Procedure

Titanium isopropoxide (1.1 mL, 3.77 mmol) was added to a mixture of 4-(5-formyl-pyridin-3-yl)-3-methoxy-benzonitrile (449 mg, 1.88 mmol) and ethanesulfonamide (226 mg, 2.07 mmol) in toluene (10 mL) at room temperature. The resulting mixture was heated to reflux for 2 h. After concentration, the residue was dissolved in THF (7 mL) and a solution of c-PrMgBr (0.5 M in THF, 18.8 mL, 9.42 mmol) was added dropwise at −40° C. The resulting mixture was stirred at −36° C. for 1 h. Saturated NH4Cl solution was added to the reaction mixture. The resulting mixture was diluted with ethyl acetate and brine and subsequently filtered. The organic layer was separated and concentrated. The residue was purified by flash column (EtOAc/Heptane=0-60%) to give the title compound (182 mg, 26% yield); ESI-MS m/z: 372 [M+1]; 1H-NMR (MeOD, 400 MHz) δ 8.59 (1H, d, J=2.0 Hz), 8.57 (1H, d, J=2.0 Hz), 8.07 (1H, t, J=2.0 Hz), 7.54 (1H, d, J=7.6 Hz), 7.49 (1H, s), 7.45 (1H, d, J=7.6 Hz), 7.42 (1H, d, 0.1=8.4 Hz), 3.89 (3H, s), 3.88 (1H, d, J=9.2 Hz), 3.01-2.88 (2H, m), 1.30-1.25 (1H, m), 1.25 (1H, t, J=7.2 Hz), 0.77-0.70 (1H, m), 0.64-0.54 (2H, m), 0.48-0.42 (1H, m)

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 2 h
  3. concentrationAfter concentration
  4. dissolutionthe residue was dissolved in THF (7 mL)
  5. filtrationsubsequently filtered
  6. customThe organic layer was separated
  7. concentrationconcentrated
  8. customThe residue was purified by flash column (EtOAc/Heptane=0-60%)

Sources & evidence

ORD record
ord-523f4a6371194fad824bda88e64b50af
Source dataset
uspto-grants-2013_02
Patent number
US08383827B2

Reaction notes

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