Reacción #87133

Ecuación de reacción

S—Phos

2-(benzyloxy)-4-bromo-1-methylbenzene

(R)-methyl 2-(tert-butoxycarbonylamino)-3-iodopropanoate

iodine

→

(S)-methyl 3-(3-(benzyloxy)-4-methylphenyl)-2-((tert-butoxycarbonyl)amino)propanoate

Rendimiento 37.1%

Disolventes

DMF

water

EtOAc

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrodried flask under N2
2. 2
   workup.STIRRINGThe reaction mixture was stirred at 60° C. for 6 h
3. 3
   Temperaturathen cooled to ambient temperature
4. 4
   Otrothe organic phase was separated
5. 5
   Lavadowashed with water (300 mL×3) and brine (300 mL×1)
6. 6
   Secadodried over anhydrous sodium sulfate
7. 7
   Concentraciónconcentrated
8. 8
   OtroThe residue was purified by flash column chromatography on silica gel (hexane/EtOAc=10:1)

Procedimiento

Dry DMF (100 mL) was added to zinc dust (7.00 g, 108 mmol) in a flame dried flask under N2. (R)-methyl 2-(tert-butoxycarbonylamino)-3-iodopropanoate (9.7 g, 29 mmol) and a catalytic amount of iodine (0.7 g, 2 mmol) were added. The mixture was stirred at ambient temperature for 0.5 h, then Pd2(dba)3 (1.9 g, 2.0 mmol), S—Phos (1.6 g, 4.0 mmol) and 2-(benzyloxy)-4-bromo-1-methylbenzene (7.40 g, 27.0 mmol) were added. The reaction mixture was stirred at 60° C. for 6 h then cooled to ambient temperature. EtOAc (500 mL) and water (500 mL) were added and the organic phase was separated, washed with water (300 mL×3) and brine (300 mL×1), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (hexane/EtOAc=10:1) to afford (S)-methyl 3-(3-(benzyloxy)-4-methylphenyl)-2-((tert-butoxycarbonyl)amino)propanoate (4.0 g, 37% yield).

Fuente