Reacción #488964

Ecuación de reacción

tert-butyl (2-hydroxyethyl)carbamate

Sodium hydride

3-chloro-2-chloromethyl-1-propene

AcOH

→

title compound

Rendimiento 59.0%

tert-Butyl 6-Methylene-1,4-oxazepane-4-carboxylate

Rendimiento 59.0%

Disolventes

THF

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroevaporated in water
2. 2
   Otroat 45-55° C.
3. 3
   Temperaturareflux condenser
4. 4
   workup.ADDITIONThe residue was poured with water (300 mL)
5. 5
   Extracciónextracted with a mixture of ethyl acetate (200 mL), hexane (100 mL) and chloroform (50 mL)
6. 6
   OtroThe organic layer was separated
7. 7
   Lavadowashed with water (2×100 mL) and brine
8. 8
   ExtracciónThe combined aqueous layer was extracted with a mixture of ethyl acetate (150 mL) and hexane (50 mL)
9. 9
   OtroThe organic layer was separated
10. 10
    Lavadowashed with water (2×100 mL) and brine
11. 11
    FiltraciónThe extracts were filtered sequentially through silica gel (25 g) and sodium sulfate (50 mL)
12. 12
    Lavadoeluting with chloroform (100 mL)
13. 13
    OtroThe filtrate was evaporated
14. 14
    workup.DISTILLATIONthe residue was distilled in vacuum

Procedimiento

60% Sodium hydride in oil (26 g, 0.65 mol, 2.17 eq) was added in one portion in argon flow at 5° C. to a solution of 3-chloro-2-chloromethyl-1-propene (35 mL, 0.3 mol, 1 eq) in dimethylformamide (500 mL). Then a solution of tert-butyl (2-hydroxyethyl)carbamate (48.3 g, 0.3 mol, 1 eq) in THF (500 mL) was added, and the reaction mixture was heated to 25° C. and stirred at this temperature for 2 h. Then the reaction mixture was neutralized with glacial AcOH (4.5 mL) and evaporated in water aspirator vacuum at 45-55° C. using a 15-cm reflux condenser. The residue was poured with water (300 mL) and extracted with a mixture of ethyl acetate (200 mL), hexane (100 mL) and chloroform (50 mL). The organic layer was separated and washed with water (2×100 mL) and brine. The combined aqueous layer was extracted with a mixture of ethyl acetate (150 mL) and hexane (50 mL). The organic layer was separated and washed with water (2×100 mL) and brine. The extracts were filtered sequentially through silica gel (25 g) and sodium sulfate (50 mL) eluting with chloroform (100 mL). The filtrate was evaporated, and the residue was distilled in vacuum to give title compound as a colorless oil (bp 76-79° C. at 0.7 mmHg) (35.8 g, 0.177 mol, 56%)

Fuente