Methanesulfonic acid, 1,1,1-trifluoro-, [bis(1-methylethoxy)phosphinyl]methyl ester synthesis

Yield:134963-85-2 96%

Reaction Conditions:

Stage #1: diisopropyl hydroxymethylphosphonatewith n-butyllithium in diethyl ether at -78; for 0.0833333 h;
Stage #2: trifluoromethane sulfonyl chloride in diethyl ether at -78; for 1.08333 h;

Steps:

4 Example 4: Synthesis of Diisopropylphosphonomethyl Trifluoromethanesulfonate

This compound was synthesized according to a known procedure: Dumbre, S. G., Jang, M., Herdewijn, P. J. Org. Chem.2013, 78, 7137-7144. To a solution of (hydroxymethyl)diisopropylphosphonate (10.0 g, 50.97 mmol) in 170 mL of dry diethyl ether at-78°C was added a solution of 1.6 M n-BuLi (35.04 mL, 56.07 mmol). The reaction mixture was allowed to stir at this temperature for 5 min and trifluoromethanesulfonyl chloride (5.97 mL, 56.07 mmol) was added dropwise over 5 minutes. The reaction mixture was stirred at this temperature for 1 h. and was quenched with sat. NH₄Cl. The organic layer was washed with brine, dried over NaSO₄, and concentrated under reduced pressure at rt gave diisopropylphosphonomethyl triflate (16.1 g, 96% yield). 1H NMR (300 MHz, CDCl₃): δ 4.774.88 [m, 2H, CH(CH₃)₂], 4.56 (d, ¹J_P,H = 8.98 Hz, 2H, PCH₂), 1.36-1.40 [m, 12H, CH(CH₃)₂]; 1³C NMR (75 MHz, CDCl₃): δ 118.4 (d, ¹J_C,F = 318.8 Hz, CF₃), 73.0 [d, ²J_P,C = 6.7 Hz, CH(CH₃)₂], 67.0 (d, ²J_P,C = 169.8 Hz, PCH₂), 23.7 [CH(CH₃)₂]. 3¹P NMR (121 MHz, CDCl₃): δ 10.0

References:

WO2016/174081,2016,A1 Location in patent:Page/Page column 22; 23