Reaction #4958

Reaction equation

ethylacetate methanol

diethylamine

diethylamine

diethylamine

ammonium hydroxide

7-chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5(4H)-one

→

white crystals

Yield 76.0%

7-Chloro-2-[2-(diethylamino)ethyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one oxalate

Yield 76.0%

Solvents

ethanol

Conditions

Workup

1. 1
   Temperaturethe mixture heated to reflux
2. 2
   workup.DISSOLUTION(Complete dissolution occurred)
3. 3
   Temperatureheating
4. 4
   Temperatureheating
5. 5
   workup.WAITcontinued for 15 hr
6. 6
   Temperatureat reflux
7. 7
   OtherSolvent was removed by rotary evaporation (60° C., 30 mm Hg)
8. 8
   Washwashed twice with dilute aqueous sodium hydroxide and once with water
9. 9
   DryingThe organic layer was dried over sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated by rotary evaporation
12. 12
    Otherazeotroped once with toluene
13. 13
    workup.ADDITIONThe oil was treated with oxalic acid in isopropyl alcohol which

Procedure

To a suspension of 7-chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5(4H)-one in 50 ml of absolute ethanol was added 2.26 ml (0.022 mole) of diethylamine and the mixture heated to reflux. (Complete dissolution occurred). After 1 hr, another 2.26 ml (0.022 mole) of diethylamine was added followed by 5.0 ml (0.049 mole) and heating continued for 2 more hours. TLC (ethylacetate/methanol/conc. ammonium hydroxide, 7:2:1, v/v/v) still showed presence of starting material; another 2.26 ml (0.022 mole) of diethylamine was added and heating continued for 15 hr at reflux. Solvent was removed by rotary evaporation (60° C., 30 mm Hg) and the residue taken up in methylene chloride, washed twice with dilute aqueous sodium hydroxide and once with water. The organic layer was dried over sodium sulfate, filtered and concentrated by rotary evaporation, and azeotroped once with toluene. The oil was treated with oxalic acid in isopropyl alcohol which yielded 6.7 g (76%) of white crystals, m.p. 163°-164° C.

Source