Reaction #312624

Reaction equation

HCl

Triethylamine

5-Bromo-2,3,4-trifluoro-benzaldehyde

trans-2,6-dimethylmorpholine

→

yellow powder

Yield 90.6%

5-Bromo-2-(2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-benzaldehyde

Yield 90.6%

Solvents

acetonitrile

Conditions

Workup

1. 1
   TemperatureThe mixture was refluxed for 24 hours
2. 2
   OtherThe acetonitrile was removed by rotoevaporation
3. 3
   Filtrationthe resulting solids were filtered
4. 4
   Washwashed with water
5. 5
   workup.DISSOLUTIONthen dissolved in THF (100 mL)
6. 6
   DryingThe solution was dried over MgSO4
7. 7
   Concentrationconcentrated to a yellow oil
8. 8
   workup.ADDITIONHexanes were added
9. 9
   Concentrationthe mixture was re-concentrated

Procedure

5-Bromo-2,3,4-trifluoro-benzaldehyde (10 g, 41.8 mmol) was dissolved in dry acetonitrile (70 mL). Triethylamine (6.4 mL, 46.0 mmol) was added, followed by trans-2,6-dimethylmorpholine (BASF, 5.3 g, 46 mmol). The mixture was refluxed for 24 hours, then cooled to room temperature, and treated with 1N HCl (58 mL). The acetonitrile was removed by rotoevaporation and the resulting solids were filtered, washed with water then dissolved in THF (100 mL). The solution was dried over MgSO4 and concentrated to a yellow oil. Hexanes were added and the mixture was re-concentrated to give 12.66 g of a yellow powder. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.26 (d, J=6.4 Hz, 6H), 2.92 (m, 2H), 3.28 (d, J=11.7 Hz, 2H), 4.15 (m, 2H), 7.78 (dd, J=7.2, 2.3 Hz, 2H), 10.32 (s, 4H).

Source