Reacción #48633

Ecuación de reacción

[2-(S)-benzyloxy-3-(S)-dibenzylamino-4-(3,5-difluorophenyl)-1-(R)-hydroxymethylbutyl]-(2-(S)-hydroxy-5-methylhexyl)-carbamic acid tert-butyl ester

tributyl phosphine

→

desired compound

Rendimiento 77.0%

5-(R)-[1-(S)-benzyloxy-2-(S)-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester

Rendimiento 77.0%

Disolventes

benzene

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroDeoxygenate the reaction mixture
2. 2
   workup.ADDITIONAdd
3. 3
   Otrodeoxygenated tetrahydrofuran (5 mL), more tributyl phosphate (130 μL), more TMAD (90 mg)
4. 4
   FiltraciónFilter
5. 5
   Lavadorinse with hexanes
6. 6
   Concentraciónconcentrate
7. 7
   Otropurify
8. 8
   Lavado(silica gel chromatography, eluting with 5:95 ethyl acetate:hexanes)

Procedimiento

Dissolve [2-(S)-benzyloxy-3-(S)-dibenzylamino-4-(3,5-difluorophenyl)-1-(R)-hydroxymethylbutyl]-(2-(S)-hydroxy-5-methylhexyl)-carbamic acid tert-butyl ester (253 mg, 347 mmol) in benzene (3 mL). Deoxygenate the reaction mixture. Add tributyl phosphine (130 μL, 520 mmol), N,N-tetramethyl azodicarboxamide (TMAD) (89.5 mg, 520 mmol) and stir at room temperature 2.5 hours. Add deoxygenated tetrahydrofuran (5 mL), more tributyl phosphate (130 μL), more TMAD (90 mg) and stir 1.5 hours. Filter, rinse with hexanes, concentrate and purify (silica gel chromatography, eluting with 5:95 ethyl acetate:hexanes) to give the desired compound (191.7 mg, 77%).

Fuente