Triisopropyl phosphite → trans 4-(Bromomethyl)-2-(diisopropyloxyphosphinoyl)-1,3-dioxolane

Temperature

0 °C

To the mixture of cis and trans 4-(bromomethyl)-2-isopropoxy-1,3-dioxolane (example 2) (6.13 g, 9:1 of isopropoxy:methoxy) was added triisopropyl phosphite (4.43 mL, 18.0 mmol, 0.66 eq.), phosphorus trichloride (0.784 mL, 8.99 mmol, 0.33 eq.) and zinc chloride (few milligrams) at 0° C. The mixture was stirred at 0° C. for 2 hr and at room temperature for 10 hr. The crude mixture of cis and trans isomers in a 2:5 ratio was purified by flash chromatography on silica gel using dichloromethane:ethyl acetate 4:1 as eluant to give the cis isomer (0.242 g), a mixture of cis and trans isomers (3.13 g) and the trans isomer (3.15 g) for a total yield of 72%. Several chromatographic purifications were performed to obtain the cis and trans isomers in pure form. ##STR21## 1H NMR (300 MHz, CDCl3) δ: 1.36 (d, 12H, J=6.1 Hz, CH(CH3)2), 3.36 (dd, 1H, J=8.0 Hz, 10.2 Hz, CHAHB Br), 3.48 (dd, 1H, J=4.4 Hz, 10.5 Hz, CHAHBBr), 3.91 (dd, 1H, J=4.6 Hz, 8.0 Hz, H-5a), 4.39 (dd, 1H, J=6.3 Hz, 8.3 Hz, H-5b), 4.63 (m, 1H, H-4), 4.80 (m, 2H, CH(CH3)2), 5.32 (d, 1H, 2JHP =30.4 Hz, H-2) ##STR22## 1H NMR (300 MHz, CDCl3) δ: 1.37 (d, 12H, J=6.1 Hz, CH(CH3)2), 3.50 (dd, 1H, J=8.9 Hz, 9.9 Hz, CHAHBBr), 3.58 (dd, 1H, J=5.3 Hz, 9.9 Hz, CHAHBBr), 4.14 (d, 2H, J=6.0 Hz, H-5), 4.41 (m, 1H, H-4), 4.80 (m, 2H, CH(CH3)2) and 5.18 (d, 1H, 2JHP =29.6 Hz, H-2).

1. additionThe crude mixture of cis and trans isomers in a 2:5 ratio
2. customwas purified by flash chromatography on silica gel
3. customto give the cis isomer (0.242 g)
4. additiona mixture of cis and trans isomers (3.13 g)
5. customto obtain the cis and trans isomers in pure form

ORD record

ord-125cf55a48c64e1791d13e98404dcb1c

Source dataset

uspto-grants-1998_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05789394