4-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehyde → HCID 46841011, compound

HRID 1846315Notes

Reaction equation

HRID 1846315 reaction equation
[NH2:1][C:2]1[C:17]([Cl:18])=[CH:16][CH:15]=[CH:14][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1)=[O:5].[OH:19][CH2:20][CH2:21][O:22][C:23]1[C:30]([CH3:31])=[CH:29][C:26]([CH:27]=O)=[CH:25][C:24]=1[CH3:32]>C(O)C.[Cu](Cl)Cl>[Br:13][C:10]1[CH:9]=[CH:8][C:7]([N:6]2[C:4](=[O:5])[C:3]3[C:2](=[C:17]([Cl:18])[CH:16]=[CH:15][CH:14]=3)[N:1]=[C:27]2[C:26]2[CH:29]=[C:30]([CH3:31])[C:23]([O:22][CH2:21][CH2:20][OH:19])=[C:24]([CH3:32])[CH:25]=2)=[CH:12][CH:11]=1

Participants

5

Reactant 2

HCID 289325784-(2-Hydroxyethoxy)-3,5-dimethylbenzaldehydeHCID 86659807HCID 86659807, compound

Product 1

HCID 46841011HCID 46841011, compound

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 702EthanolSolvent

Procedure

To a solution of 2-amino-N-(4-bromophenyl)-3-chlorobenzamide (0.52 g, 1.60 mmol) and 4-(2-hydroxyethoxy)-3,5-dimethylbenzaldehyde (0.31 g, 1.60 mmol) in anhydrous ethanol (20 mL), anhydrous copper (II) chloride (0.86 g, 6.40 mmol) was added and the reaction mixture was refluxed for 16 hours. The solvent was evaporated in vacuo, water (100 mL) was then added, and the product was extracted with ethyl acetate (200 mL). The organic phase was separated, washed with water (2×100 mL), then brine (100 mL), and dried over anhydrous Na2SO4. The solvent was evaporated, and the crude compound was purified by the Simpliflash system (20-40% ethyl acetate in hexanes as eluent), to give the title compound as a white solid. Yield 0.37 g (46%). MP 185-186° C. 1H-NMR (400 MHz, CDCl3) 8.25 (d, J=8.20 Hz, 1H) 7.89 (d, J=7.42 Hz, 1H) 7.56-7.34 (m, 3H) 7.03 (t, J=4.29 Hz, 4H), 4.06-3.87 (m, 2H) 3.87-3.74 (m, 2H) 2.18 (s, 6H) 2.11-1.95 (m, 1H). MS (ES+) m/z: 499.36, 501.38 (100%), 503.33.

Workup

  1. temperaturethe reaction mixture was refluxed for 16 hours
  2. customThe solvent was evaporated in vacuo, water (100 mL)
  3. additionwas then added
  4. extractionthe product was extracted with ethyl acetate (200 mL)
  5. customThe organic phase was separated
  6. washwashed with water (2×100 mL)
  7. dry with materialbrine (100 mL), and dried over anhydrous Na2SO4
  8. customThe solvent was evaporated
  9. customthe crude compound was purified by the Simpliflash system (20-40% ethyl acetate in hexanes as eluent)

Sources & evidence

ORD record
ord-d88a01fe356747a28a4410e98bde50b7
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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