Reaction #44794

Reaction equation

sodium bicarbonate

methyl 4-[(hexahydro-1H-diazepin-1-yl)methyl]benzoate

1-(2-iodoethoxy)-4-(benzyl)benzene

triethylamine

→

methyl 4-[[hexahydro-4-[2-[4-(phenylmethyl)phenoxy]ethyl]-1H-1,4-diazepin-1-yl]methyl]benzoate

Yield 27.3%

Solvents

THF

Conditions

Workup

1. 1
   Temperatureheated
2. 2
   Temperatureat reflux for 5 hours
3. 3
   TemperatureAfter cooling
4. 4
   ExtractionThe mixture was extracted with ethyl acetate
5. 5
   WashThe organic layer was washed with brine
6. 6
   Dryingdried over sodium sulfate
7. 7
   Concentrationconcentrated under reduced pressure

Procedure

A mixture of methyl 4-[(hexahydro-1H-diazepin-1-yl)methyl]benzoate (109 mg, 0.44 mmol) and 1-(2-iodoethoxy)-4-(benzyl)benzene (120 mg, 0.44 mmol) in THF (4 mL) was treated with triethylamine (112 μl, 0.80 mmol) and heated at reflux for 5 hours. After cooling, the mixture was treated with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. Flash chromatography gave 55 mg of methyl 4-[[hexahydro-4-[2-[4-(phenylmethyl)phenoxy]ethyl]-1H-1,4-diazepin-1-yl]methyl]benzoate; 1H NMR (300 MHz, CDCl3) δ 7.98 (d, 2H), 7.42 (d, 2H), 7.28 (dd, 2H), 7.17 (d, 2H), 7.18 (dd, 1H), 7.09 (d, 2H), 6.82 (d, 2H), 4.05 (t, 2H), 3.92 (s, 2H), 3.91 (s, 3H), 3.69 (s, 2H), 2.97 (t, 2H), 2.88 (m, 2H), 2.84 (m, 2H), 2.69 (m, 4H), 1.81 (m, 2H) ppm.

Source