Iodine → (S)-methyl 2-(benzyloxycarbonylamino)-3-(1H-indol-5-yl)propanoate

To a suspension of zinc (2.53 g, 38.8 mmol) in DMF (20 mL) was added I2 (1.10 g, 4.15 mol) followed by addition of a solution of (R)-methyl 2-(benzyloxycarbonylamino)-3-iodopropanoate (4.70 g, 13.0 mmol) in DMF (20 mL). The mixture was stirred at ambient temperature for 5 min and heated at 35° C. for 40 min. Then a solution of 5-bromo-1H-indole (3.00 g, 15.5 mmol) in DMF (10 mL), Pd2(dba)3 (0.25 g, 0.27 mmol) and S—Phos (0.25 g, 0.60 mmol) were added. The reaction mixture was stirred at 50° C. under nitrogen overnight and then cooled to ambient temperature. Brine (500 mL) was added and the resulting mixture was extracted with EtOAc (200 mL×3). The organics were combined, washed with brine (300 mL) and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=10:1 to 5:1) to afford (S)-methyl 2-(benzyloxycarbonylamino)-3-(1H-indol-5-yl)propanoate as a viscous oil (3.27 g, 60% yield).

1. temperatureheated at 35° C. for 40 min
2. stirringThe reaction mixture was stirred at 50° C. under nitrogen overnight
3. temperaturecooled to ambient temperature
4. extractionthe resulting mixture was extracted with EtOAc (200 mL×3)
5. washwashed with brine (300 mL)
6. concentrationconcentrated
7. customThe residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=10:1 to 5:1)

ORD record

ord-7ddbbc0e8fed4be386b1454272ad4211

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434761B2