Reaktion #4935

Reaktionsgleichung

pyrazole

sodium hydride

pyrazole

pyrazole

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

sodium hydride

→

2,3-Dihydro-4-methyl-2-[2-(1H-pyrazol-1-yl)ethyl]pyrido[3,2-f][1,4]oxazepin-5(4H)-one

Lösungsmittel

dimethylformamide

dimethylformamide

dimethylformamide

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe flask was sealed
2. 2
   workup.ADDITIONwas added to the reaction solution
3. 3
   workup.STIRRINGstirred overnight
4. 4
   workup.ADDITIONwas added
5. 5
   workup.STIRRINGthe reaction stirred overnight
6. 6
   SonstigeDimethylformamide was removed by rotary evaporation (80° C., vacuum pump)
7. 7
   Waschenwas washed with dilute aqueous sodium hydroxide (1×50 ml)
8. 8
   Trocknendried over anhydrous sodium sulfate
9. 9
   Einengenconcentrated by rotary evaporation (70° C., water aspirator)
10. 10
    SonstigeThe material was purified by high pressure liquid chromatography, 95:5 by volume ethanol
11. 11
    workup.ADDITIONThe fractions containing the desired product
12. 12
    Einengenwere concentrated by rotary evaporation (70° C., water aspirator)
13. 13
    SonstigeCrystallization
14. 14
    Temperaturupon cooling
15. 15
    SonstigeThe crystals were collected
16. 16
    Sonstigerecrystallized from ethanol

Vorschrift

To a suspension of sodium hydride (1.2 g active, 0.05 mole) in dimethylformamide (15 ml) was added dropwise a solution of pyrazole (3.10 g, 0.045 mole) in dimethylformamide (15 ml). The resulting solution was then added to a solution of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5(4H)-one (9.12 g, 0.038 mole) in 30 ml of dimethylformamide. The flask was sealed and stirred overnight. Because the reaction had not yet gone to completion at this point, pyrazole (3.12 g, 0.045 mole) was added to the reaction solution and stirred overnight. The reaction was still not complete and another suspension of sodium hydride (0.5 g active, 0.021 mole) and pyrazole (1.5 g, 0.022 mole) in dimethylformamide (10 ml) was added and the reaction stirred overnight. The reaction appeared to be complete. Dimethylformamide was removed by rotary evaporation (80° C., vacuum pump), and the residue taken up in chloroform (100 ml) which was washed with dilute aqueous sodium hydroxide (1×50 ml), dried over anhydrous sodium sulfate and concentrated by rotary evaporation (70° C., water aspirator). The material was purified by high pressure liquid chromatography, 95:5 by volume ethanol:methanol on a silica gel column. The fractions containing the desired product were concentrated by rotary evaporation (70° C., water aspirator). Crystallization ensued upon cooling. The crystals were collected and recrystallized from ethanol. The yield was 1.5 (14.5%), m.p. 132°-134° C.

Quelle