Реакция #4917

Уравнение реакции

triphenylphosphine

carbon tetrachloride

sodium hydride

triphenylphosphine

carbon tetrachloride

N-methyl-3-pyrrolidinol

3,5-dichloropyridine-4-carboxylic acid

→

desired product

6-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[4,3-f]-1,4-oxazepin

triphenylphosphine oxide

Растворители

triethylamine

dimethylformamide

dimethylformamide

Условия реакции

Обработка

1. 1
   Температураto maintain 60° C
2. 2
   workup.ADDITIONSubsequent to this addition
3. 3
   Температураthe mixture was heated to 75° C. for 3 hr
4. 4
   ДругоеThe solvent was then removed by rotary evaporation (60° C., 5 mm)
5. 5
   workup.ADDITIONhydrogen chloride added until a pH of 3
6. 6
   Температураthe entire mixture heated to reflux
7. 7
   Другоеfollowed by the same increments 1 hr
8. 8
   ПромывкаThe reaction mixture was washed with 6×50 ml of 3N hydrochloric acid
9. 9
   Сушкаdried over sodium sulfate
10. 10
    Фильтрацияfiltered
11. 11
    Концентрированиеconcentrated by rotary evaporation
12. 12
    workup.ADDITIONTo the residue was added ethyl acetate, which

Методика

To a suspension of 2.1 g (60% in oil, 0.052 mole) of sodium hydride in 125 ml of dimethylformamide heated to 60° C. under a nitrogen gas blanket was added a solution of 2.65 g (0.026 mole) of N-methyl-3-pyrrolidinol and 5.0 g (0.026 mole) of 3,5-dichloropyridine-4-carboxylic acid in 40 ml of dimethylformamide dropwise at such a rate as to maintain 60° C. Subsequent to this addition, the mixture was heated to 75° C. for 3 hr. The solvent was then removed by rotary evaporation (60° C., 5 mm). The entire solid residue was suspended in 150 ml methylene chloride and hydrogen chloride added until a pH of 3 was reached. To the resulting mixture was added 15 g (0.057 mole) of triphenylphosphine and 15 g carbon tetrachloride and the entire mixture heated to reflux. After 1 hr, 7.5 g (0.029 mole) of triphenylphosphine and 7.5 g carbon tetrachloride were added, followed by the same increments 1 hr later. The reaction was driven to completion by adding 20 ml of triethylamine. The reaction mixture was washed with 6×50 ml of 3N hydrochloric acid, dried over sodium sulfate, filtered and concentrated by rotary evaporation. To the residue was added ethyl acetate, which caused much tarry material to fall out of solution, leaving the desired product and triphenylphosphine oxide in solution. The mixture was chromatographed by column chromatography using silica gel as the stationary phase and ethyl acetate as eluent. Similar fractions were combined and ethyl acetate removed by rotary evaporation, yielding 0.6 g (7%), of white crystals, m.p. 134°-38° C.

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