Acetic Acid → 1-(5-bromo-4-methylpyridin-2-yl)-2,2,2-trifluoro-N-(4-methoxybenzylidene)ethanamine

HRID 468922Notes

Reaction equation

HRID 468922 reaction equation
[Br:1][C:2]1[C:3]([CH3:15])=[CH:4][C:5]([C:8](O)(O)[C:9]([F:12])([F:11])[F:10])=[N:6][CH:7]=1.[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][NH2:23])=[CH:20][CH:19]=1.C(O)(=O)C>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:3]([CH3:15])=[CH:4][C:5]([CH:8]([N:23]=[CH:22][C:21]2[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[C:9]([F:12])([F:11])[F:10])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 754524-MethoxybenzylamineHCID 711150501-(5-Bromo-4-methylpyridin-2-yl)-2,2,2-trifluoroethane-1,1-diol

Product 1

HCID 711153411-(5-bromo-4-methylpyridin-2-yl)-2,2,2-trifluoro-N-(4-methoxybenzylidene)ethanamineYield 74.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
110 °C

Procedure

A solution of 1-(5-bromo-4-methylpyridin-2-yl)-2,2,2-trifluoroethane-1,1-diol (163.1 mg; 0.5702 mmol) in 2.0 mL toluene was added at room temperature to a solution of 4-methoxybenzylamine (118 μL; 0.858 mmol) and acetic acid (49 μL; 0.854 mmol) in 2.0 mL toluene. A scoop of oven-dried 3A molecular sieves was added, and the reaction mixture heated at 110° C. for 3 days. The mixture was poured into saturated aqueous sodium bicarbonate and extracted twice with dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The crude product was purified via flash chromatography on silica gel (24 g silica, solvent gradient: 0-100% ethyl acetate in dichloromethane) to yield 164.2 mg of the title compound. LCMS (ESI): M-(4-methoxybenzaldehyde)+H=269.2; 1H NMR (400 MHz, DMSO) δ 8.69 (s, 1H), 8.57 (s, 1H), 7.80 (d, J=8.7 Hz, 2H), 7.66 (s, 1H), 7.05 (d, J=8.7 Hz, 2H), 5.28 (q, J=8.0 Hz, 1H), 3.82 (s, 3H), 2.41 (s, 3H).

Workup

  1. dry with materialA scoop of oven-dried 3A molecular sieves
  2. additionwas added
  3. additionThe mixture was poured into saturated aqueous sodium bicarbonate
  4. extractionextracted twice with dichloromethane
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified via flash chromatography on silica gel (24 g silica, solvent gradient: 0-100% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-37d028984d9b4bddb596867c80a41e12
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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