Reaktion #87075

Reaktionsgleichung

S—Phos

4-bromo-2-methoxypyridine

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

iodine

→

(S)-methyl 2-(tert-butoxycarbonylamino)-3-(2-methoxypyridin-4-yl)propanoate

Ausbeute 73.0%

Lösungsmittel

DMF

water

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedried bottom flask under N2
2. 2
   TemperaturThe reaction mixture was heated at 60° C. for 6 h
3. 3
   Temperaturcooled to ambient temperature
4. 4
   SonstigeThe organic phase was separated
5. 5
   Waschenwashed with water (300 mL×3) and brine (300 mL×1)
6. 6
   Trocknendried over anhydrous sodium sulfate
7. 7
   Einengenconcentrated
8. 8
   SonstigeThe residue was purified by flash column chromatography on silica gel (hexane/EtOAc=2:1)

Vorschrift

Dry DMF (30 mL) was added to zinc dust (2.78 g, 42.6 mmol) in a flame dried bottom flask under N2. (R)-Methyl 2-(tert-butoxycarbonylamino)-3-iodopropanoate (3.85 g, 11.7 mmol) was added followed by a catalytic amount of iodine (1.06 g, 0.10 mmol). The mixture was stirred at ambient temperature for 0.5 h. Pd2(dba)3 (487 mg, 0.050 mmol), S—Phos (437 g, 0.100 mmol) and 4-bromo-2-methoxypyridine (2.00 g, 10.6 mmol) were added. The reaction mixture was heated at 60° C. for 6 h and then cooled to ambient temperature. EtOAc (200 mL) and water (200 mL) were added. 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=2:1) to afford (S)-methyl 2-(tert-butoxycarbonylamino)-3-(2-methoxypyridin-4-yl)propanoate (2.4 g, 73% yield).

Quelle