Reacción #48627

Ecuación de reacción

benzyl bromide

sodium hydride

benzyl bromide

4-(R)-[2-(S)-amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

sodium hydride

→

desired compound

4-(R)-[1-(S)-benzyloxy-3-(3-benzyloxyphenyl)-2-(S)-dibenzylaminopropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Disolventes

ethyl acetate

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónconcentrate
2. 2
   workup.STIRRINGstir overnight at 65° C
3. 3
   Otroquench with water (300 mL)
4. 4
   Lavadowash with water, and saturated aqueous sodium chloride
5. 5
   ExtracciónExtract the aqueous washes with ethyl acetate
6. 6
   Secadodry (magnesium sulfate)
7. 7
   Filtraciónfilter
8. 8
   Otropurify twice
9. 9
   Lavado(silica gel chromatography, eluting with 5:95 to 10:90 ethyl acetate:hexanes)

Procedimiento

Add tricaprylmethylammonium chloride (Aliquat® 336) (4.5 g, 11.2 mmol) and tetrabutylammonium bromide (TBAB) (5.7 g, 15.7 mmol) to a solution of 4-(R)-[2-(S)-amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (16.45 g, crude) in tetrahydrofuran (200 mL). Add portionwise 95% sodium hydride (2.6 g, 90 mmol) and stir for 10 minutes. Add benzyl bromide (13.4 mL, 112.5 mmol) and heat at 60° C. for 40 minutes and concentrate. Add more 95% sodium hydride (5.4 g, 225 mmol) and benzyl bromide (27 mL, 225 mmol) in tetrahydrofuran (−5 mL) and stir overnight at 65° C. Dilute with ethyl acetate, quench with water (300 mL), wash with water, and saturated aqueous sodium chloride. Extract the aqueous washes with ethyl acetate, comvine the organic layers, dry (magnesium sulfate), filter and purify twice (silica gel chromatography, eluting with 5:95 to 10:90 ethyl acetate:hexanes) to give the desired compound as an orange residue (16.01 g, 49%).

Fuente