Reaction Steps
To a solution of diethylphosphonoacetaldehyde diethylacetal (4.20 g, 16.5 mmol) and (2R)-3-bromo-1,2-propanediol (example 90) (3.00 g, 19.4 mmol, 1.2 eq.) in toluene (30 mL) was added pTSA (few crystals). The mixture was stirred at reflux for 50 hr. After, the solution was cooled to room temperature, and a saturated solution of sodium bicarbonate was added, and the aqueous phase was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulphate and evaporated under reduced pressure. The crude material was pure by TLC and NMR, and gave 5.06 g of the compound in a 97% yield. 1H NMR (300 MHz, CDCl3) δ: 1.33 (t, 6H, J=7.0 Hz, CH3), 2.20 (dd, 0.66H, J=5.4 Hz, 2JHP=18 Hz, CH2P for trans), 2.25 (dd, 1.33H, J=5.2 Hz, 2JHP=18.7 Hz, CH2P for cis), 3.32 (2dd, 1H, J=7.9 Hz, 10.2 Hz, CHAHBBr), 3.42 and 3.48 (2dd, 1H, J=4.8 Hz, 10.2 Hz, CHAHBBr), 3.74 (dd, 0.33H, J=6.4 Hz, 8.8 Hz, H-5a for trans), 3.99 (d, 1.33H, J=5.2 Hz, H-5 for cis), 4.13 (m, 4H, CH2), 4.26 (dd, 0.33H, J=6.4 Hz, 8.8 Hz, H-5b for trans), 4.35 (m, 1H, H-4), 5.24 (dt, 0.66H, J=5.2 Hz, 3JHP=4.7 Hz, H-2 for cis), 5.37 (dt, 0.33H, J=5.2 Hz, 3JHP=5.2 Hz, H-2 for trans).
