| 75% |
In diethyl ether; at -10 - 20℃; for 20.5h;Inert atmosphere; |
The first two steps to provide 2-chloro-l ,3,2-dioxaphospholane oxide were previously described and carried out according to the methods of Lucas7 and Edmundson 8.Methoxyethyl- l ,3,2-dioxaphospholane oxide was prepared as described in Example 1. The 3- (dimethylamino)propyl methacry.ate was synthesised according to the procedure described in Scheme II.3-(dimethylamino) propanol (0.02 mol) was blended in an oven dried round bottom flask, flushed with Ni, with anhydrous diethyl ether (60mL) and triethylamine (0.04 mol). The mixture was cooled down to -10C. Methacryloyl chloride (0.02 mol) in 7ml anhydrous diethyl ether was added dropwise to the reaction mixture over 30 min, maintaining the temperature at - 10C under N2. After the addition, the mixture was stirred and allowed to warm up slowly to room temperature overnight (20h). The triethylammonium chloride salt was filtered through celite and glass wool and washed thoroughly with diethyl ether. The solvent was removed via rotary evaporation and the product was purified by distillation under reduced pressure (40C at 0.5 mm Hg) to afford a yield of 75%. NMR (400 MHz, CDCI3) delta ppm: 1 .85 (dt, J=8 and J=8, 2H, -CH2-CHj-CH ), 1 .95 (s, 3H, CH3- C=CH2), 2.22 (s, 6H, -N(CH 2), 2.36 (t, J=8. 2Eta, -N-CH?-), 4.20 (t, J=8, 2Eta, -C/_ 0-C=0), 5.55 (d, J=4, 1Eta, Ci¾=C-) and 6.10 (d, J=4, 1 Eta, CH2=C-) ; UC NMR ( 100 MHz, CDC13) delta ppm: 18.30 (CH3-C=CH2-), 27.00 (-CH2-CH2-CH2-), 45.47 (CH3-N-CH3), 56.30 (CH2-N-(CH3)2), 63.02 (-CH2- O-OO), 125.24 ( H2=C-), 136.43 (CH2=C-CH3).. 167.40 (0-C=0); FT-IR vmax / cm' 1 : 2934 (CH3, CH2 St.), 1732 (0-C=0 st.), 1677 (C=C st), 1 154 (C-C-N bend), 1036 (C-O-C St.); ESI LCMS for C9H 1802N found m/z 172.1329 (M+H]+ (calculated 172.1338).The methoxyethyl-l ,3,2-dioxaphospholane oxide obtained ( 1 equivalent) was blended in an oven- dried glass bottle (SCHOTT Duran lOOmL) with previously synthesised 3-(dimethylamino)propyl meihacrylate ( 1 equivalent) and 2000 ppm of 2-methoxyphenol (Aldrich) with freshly distilled acetonitriie (2.6 molar). The mixture was stirred at 120C for 24 hours. At the completion of the reaction, most of the acetonitriie was removed in a stream of nitrogen. The remaining yellow/brown oil was dissolved in a minimum amount of anhydrous methanol and reprecipitated from anhydrous diethyl ether. This process was repeated 3 times. The crude oil was purified by silica gel column chromatography using a mixture of acetonitrile/methanoVwater in a ratio of 4/171 , respectively, yielding a transparent viscous oil. The oil was completely dried from water when dissolved in a small amount of acetoiiitrile and dried over MgS04 for 1 hour. The compound was dried under a stream of N and finally under high vacuum (yield = 46%). NMR (400 MHz. D20) delta ppm: 1.81 (s, 3H, CH,-OCH2-), 2.1 1 to 2. 18 (m, 2H, CH2-CV/ CH2-), 3.08 (s, 6H, CHjW-CHs), 3.28 (s, 3H, C fj-O-), 3.42 to 3.46 (m, 2H, -CJfc-N*-), 3.53 to 3.58 (m, 4H, -CH2-O and -CH2-N+-), 3.87 to 3.91 (m, 2Eta, -CH O-P=0), 4.16 to 4.18 (m, 4Eta, -CH O-P=0 and -CH2-0-C=0), 5.62 (d, J=4, Iota Eta, CH2=C-) and 6.03 (d, J=4, 1 Eta, CH2=C-); 31P NMR ( 162 MHz, D20) delta ppm: -0.32 ; l 3C NMR ( 100 MHz, D20) delta ppm: 17.27 (CH3-C=CH2-), 21.76 (CH CH2-CH2- ), 51.45 (CH3-N+-CW3), 58.06 (CH3-0-CH2-), 59.13 (-CH2-0-C=0), 61.85 (-CH2-0-P=0), 62.78 (- CHi-W-CH2-)t 64.67 (-CH2-N+-CH2-), 64.73 (-CH2-0-P=0), 71.46 (CH3-0-CH2-), 127.01 (CH2=C- ), 135.60 (CH2=C-CH3), 169.44 (O-OO); FT-IR vmax / cm'1 : 2959 (CH2 St.), 1717 (0-C=0 St.), 1637 (C=C st.), 1456 (-N^CH^ def.), 1298 (P=0 St.), 1239 (C-O-C St.), 1 160 (C-N bend), 1059 (P- O-C St.), 950 (-N(CH3)2 St.), 842 (CH2), 786 (CH2); ESI LCMS for C4H29NO7P found /z 354.1679 [M+H]+ (calculated 354.1682) and CMH2SN07PNa found m 376.1497 [M+Na]+ (calculated 376.1 501). |
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