Uses
Diethyl (bromodifluoromethyl)phosphonate is used as a reactant for the preparation of phosphopeptide mimetic prodrugs targeted to Src homology 2 (SH2) domain of signal transducer and activator of transcription 3 (Stat3), synthesis of Mycobacterium tuberculosis protein tyrosine phosphatase inhibitory difluoromethylphosphonic acid derivatives via multi step synthesis with Suzuki coupling and resolution as key steps and P-C bond cleavage on basic hydrolysis.
Uses
Efficient difluoroalkylation of aryl boronic acids via palladium catalysis. Novel, moisture-stable bromodifluoromethylated phosphonate, ester, and amide. Efficient coupling with aryl boronic acids via Pd catalysis.
Synthesis Reference(s)
The Journal of Organic Chemistry, 49, p. 3437, 1984
DOI: 10.1021/jo00192a056
reaction suitability
reaction type: C-C Bond Formation
Synthesis
Dibromodifluoromethane (209.8 g, 1 mol) was slowly added dropwise to a solution of triethyl phosphite (153.5 g, 0.925 mol) in anhydrous ether (450 mL) equipped with a magnetic stirrer under nitrogen protection. After the dropwise addition, the reaction system was slowly warmed to room temperature and subsequently heated to reflux for 20 hours. Upon completion of the reaction, the volatile solvent was removed by distillation under reduced pressure and the fraction with a boiling point of 50-52 °C (1 mmHg) was collected to afford the colorless liquid product diethyl (bromodifluoromethyl) phosphonate (256.3 g, 96% yield). The structure of the product was confirmed by 1H NMR (CDCl3): δ 4.35 (m, 4H), 1.35 (m, 6H); 13C NMR (CDCl3): δ 122.9, 119.8, 118.6, 115.4, 114.2, 111.1, 66.59, 66.50, 16.56, 16.48.
References
[1] Journal of Organometallic Chemistry, 1997, vol. 529, # 1-2, p. 267 - 278
[2] Phosphorus, Sulfur and Silicon and Related Elements, 1997, vol. 122, p. 247 - 259
[3] Patent: US2004/225146, 2004, A1. Location in patent: Page 4
[4] Journal of Fluorine Chemistry, 2011, vol. 132, # 10, p. 815 - 828
[5] Patent: WO2006/78698, 2006, A1. Location in patent: Page/Page column 64-65
