Reaction #1973908

Reaction equation

hydrogen

lithium

hydride

2-Benzyloxy-N-(2-chloro-5-methoxy-phenyl) acetamide

lithium aluminium hydride

→

(2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl) amine

Yield 101.7%

Solvents

THF

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   TemperatureThe reaction was then heated
3. 3
   Temperatureto reflux for 4 h
4. 4
   Otherto stand at RT over the weekend
5. 5
   OtherThe reaction was then quenched by the dropwise addition of water (50 mL) to the stirred solution
6. 6
   Temperatureto reflux
7. 7
   ConcentrationThe reaction was then concentrated in vacuum to a slurry
8. 8
   workup.ADDITIONWater (200 mL) and ethyl acetate (200 mL) were added
9. 9
   FiltrationThe reaction was then filtered through celite
10. 10
    Otherto remove the precipitated aluminium hydroxide
11. 11
    Otherthe ethyl acetate solution was separated
12. 12
    Dryingdried over magnesium sulfate
13. 13
    Concentrationconcentrated in vacuo

Procedure

2-Benzyloxy-N-(2-chloro-5-methoxy-phenyl) acetamide (2) (18.9 g, 62.0 mmol) in THF (100 mL) was stirred and lithium aluminuim hydride (4.9 g, 130.0 mmol) was added slowly over 15 min. There was a rapid evolution of hydrogen gas as the first of the lithium aluminium hydride was added. The reaction was then heated to reflux for 4 h and allowed to stand at RT over the weekend. The reaction was then quenched by the dropwise addition of water (50 mL) to the stirred solution. There was a violent evolution of hydrogen causing the reaction mixture to reflux. The reaction was then concentrated in vacuum to a slurry. Water (200 mL) and ethyl acetate (200 mL) were added and the mixture vigorously shaken. The reaction was then filtered through celite to remove the precipitated aluminium hydroxide and the ethyl acetate solution was separated, dried over magnesium sulfate and concentrated in vacuo to afford 18.4 g (quantitative) of (2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl) amine (3) as a gum. The structure was confirmed by 13C NMR (75 MHz, CDCl3) δC 43.3, 55.3, 68.2, 73.0, 98.1, 101.8, 111.6, 127.6, 127.7, 128.4, 129.3, 137.9, 144.8, and 159.5.

Source