Reacción #48303

Ecuación de reacción

DDQ

Acetyl chloride

(4S,5S)-Tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-2,2-dimethyl-4-(pyridin-4-ylmethyl)oxazolidine-3-carboxylate

METHYLMAGNESIUM BROMIDE

→

title compound

(4S,5S)-tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-2,2-dimethyl-4-((2-methylpyridin-4-yl)methyl)oxazolidine-3-carboxylate

Disolventes

ethyl acetate

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   Temperaturaat 0° C. and then warmed to RT
3. 3
   Otroquenched with saturated ammonium chloride
4. 4
   workup.ADDITIONdiluted with EtOAc and water
5. 5
   OtroThe layers were separated
6. 6
   Extracciónthe aqueous layer was extracted with EtOAc
7. 7
   LavadoThe combined organic layers were washed with a 9:1 aqueous solution of saturated ammonium chloride/ammonium hydroxide, water, brine
8. 8
   Secadodried over sodium sulfate
9. 9
   workup.DISSOLUTIONThe crude product was dissolved in isopropylacetate (4 mL)
10. 10
    workup.ADDITIONwas added
11. 11
    TemperaturaAfter 30 minutes the reaction was cooled
12. 12
    Lavadowashed twice with saturated sodium bicarbonate, once with water, brine
13. 13
    Secadodried over sodium sulfate
14. 14
    Concentraciónconcentrated

Procedimiento

(4S,5S)-Tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-2,2-dimethyl-4-(pyridin-4-ylmethyl)oxazolidine-3-carboxylate (0.150 g, 0.344 mmol) was dissolved in THF (3.5 mL) and cooled to 0° C. Acetyl chloride (0.0256 ml, 0.361 mmol) was added and the reaction was stirred 30 minutes before METHYLMAGNESIUM BROMIDE (0.294 ml, 0.412 mmol) was added. The reaction was stirred 1 hr. at 0° C. and then warmed to RT and quenched with saturated ammonium chloride and diluted with EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with a 9:1 aqueous solution of saturated ammonium chloride/ammonium hydroxide, water, brine, and dried over sodium sulfate. The crude product was dissolved in isopropylacetate (4 mL) and heated to 50° C. before DDQ (0.117 g, 0.515 mmol) was added. After 30 minutes the reaction was cooled and diluted with ethyl acetate and washed twice with saturated sodium bicarbonate, once with water, brine, and dried over sodium sulfate. The mixture was passed through a plug of silica gel with 2:1 Hexanes/EtOAc and concentrated to afford the title compound, MS m/z: 451.3(100%, M+1)).

Fuente