4-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehyde → HCID 46840740, compound

HRID 1846284Notes

Reaction equation

HRID 1846284 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH2:15][CH3:16])[CH3:14])=[CH:9][CH:8]=1)=[O:5].[OH:22][CH2:23][CH2:24][O:25][C:26]1[C:33]([CH3:34])=[CH:32][C:29]([CH:30]=O)=[CH:28][C:27]=1[CH3:35]>C(O)C>[CH:13]([C:10]1[CH:9]=[CH:8][C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[CH:20][CH:19]=[C:18]([F:21])[CH:17]=3)[N:1]=[C:30]2[C:29]2[CH:32]=[C:33]([CH3:34])[C:26]([O:25][CH2:24][CH2:23][OH:22])=[C:27]([CH3:35])[CH:28]=2)=[CH:12][CH:11]=1)([CH2:15][CH3:16])[CH3:14]

Participants

4

Reactant 2

HCID 289325784-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehydeHCID 43702109HCID 43702109, compound

Product 1

HCID 46840740HCID 46840740, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Anhydrous CuCl2 (0.21 g, 1.6 mmol) was added to a solution of 2-amino-N-(4-sec-butylphenyl)-5-fluorobenzamide (0.15 g, 0.52 mmol), and 4-(2-hydroxyethoxy)-3,5-dimethyl-benzaldehyde (0.12 g, 0.63 mmol) in ethanol (30 mL). The resulting green solution was heated at reflux for 3 hours. After cooling to room temperature, the mixture was concentrated under vacuum. The residue was stirred with water (20 mL), and extracted with ethyl acetate (2×25 mL). The organic layer was separated, washed with brine, and dried over Na2SO4. The solvent was evaporated under vacuum, and the residue was purified by flash column chromatography on a Biotage (25 M silica column) using a gradient of hexane:ethyl acetate (8:2 to 5:5) mixture as eluent to afford the title compound. Yield: 0.19 g (77%). MP 70-72° C. 1H-NMR (400 MHz, CDCl3): 7.99 (m, 1H), 7.82 (m, 1H), 7.53 (m, 1H), 7.15 (m, 2H), 7.09 (d, 2H), 6.97 (s, 2H), 3.91 (m, 2H), 3.78 (m, 2H), 2.59 (m, 1H), 2.15 (s, 6H), 2.02 (t, 1H), 1.54 (m, 2H), 1.21 (d, 2H), 0.73 (t, 3H).

Workup

  1. temperatureThe resulting green solution was heated
  2. temperatureat reflux for 3 hours
  3. concentrationthe mixture was concentrated under vacuum
  4. extractionextracted with ethyl acetate (2×25 mL)
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. customThe solvent was evaporated under vacuum
  9. customthe residue was purified by flash column chromatography on a Biotage (25 M silica column)

Sources & evidence

ORD record
ord-7c85acf729584d638c12adf52d6d8109
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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