Imidazole → methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoate

Temperature

0 °C

A mixture of triphenylphosphine (131 g, 0.500 mol) and imidazole (34 g, 0.50 mol) in DCM (600 mL) was cooled to 0° C. and iodide (127 g, 0.50 mol) was added in small portions over 0.5 h. The cooling bath was removed and the mixture was stirred for 0.5 h. After the mixture was re-cooled to 0° C., a solution of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-hydroxypropanoate (73 g, 0.33 mol) in DCM (300 mL) was added dropwise. After the addition, the cooling bath was removed and the mixture was allowed to warm to ambient temperature and stirred for 1.5 h. The mixture was filtered and the filtrate was concentrated to remove most of the solvent. MTBE (400 mL) was added to the residue and the mixture was filtered to remove triphenylphosphine oxide. The filtrate was concentrated and the residue was purified by flash column chromatography on silica gel to afford (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (74.0 g, 68% yield) as a colorless solid.

1. customThe cooling bath was removed
2. temperatureAfter the mixture was re-cooled to 0° C.
3. additionAfter the addition
4. customthe cooling bath was removed
5. temperatureto warm to ambient temperature
6. stirringstirred for 1.5 h
7. filtrationThe mixture was filtered
8. concentrationthe filtrate was concentrated
9. customto remove most of the solvent
10. additionMTBE (400 mL) was added to the residue
11. filtrationthe mixture was filtered
12. customto remove triphenylphosphine oxide
13. concentrationThe filtrate was concentrated
14. customthe residue was purified by flash column chromatography on silica gel

ORD record

ord-c4c62557219c49f4894c4f195aa68a46

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434761B2