反应详情

温度

60 °C

4-(4-Hydroxyphenyl)piperazine (0.356 g, 2 mmol) is added to a stirred a pentane washed suspension of 60% NaH (0.088 g, 2.2 mmol) in DMF (5 mL) under N2 and the reaction mixture was heated to 60° C. for approximately 10 min (until the effervescence ceased). To the clear dark solution 3, 3-diphenyl-1-methanesulfonyloxypropane in NMP (3 mL) is added at once and the reaction mixture is heated to 90° C. over the weekend. (~65 h) NMP is removed in vacuo at 100° C. and the residue is taken up in CH2Cl2. The solution is washed (H2 O), separated, dried (Na2SO4) and evaporated in vacuo. The residue is purified by chromatography on silica using increasing proportion of MeOH in CH2Cl2 containing 0.5% Et3N. Two major products are isolated. The less polar one eluted with 4% MeOH / CH2Cl2 (0.5% Et3N) as an oil (0.19 g) is characterized as the N, O-dialkylated product . MS 568 (MH+). The more polar product (desired), is eluted with 10% MeOH/CH2Cl2 and obtained as an oil, 0.52 g (70%), which crystallizes in to a waxy solid upon drying at 50° C. in vacuo : mp 114°-116° C. This compound is converted in to an oxalate salt by treatment with one equivalent of oxalic acid in i-PrOH and recrystallization from the same solvent: mp, decomposing above 170° C. 1NMR (CDCl3) d 7.60 (d, 2H), 7.40-7.24 (m, 8H), 7.19 (t, 2H), 7.06 (d, 2H), 5.71 (br s, H2O / H+) 4.22 (t, 2H), 4.90 (t, 2H) 3.82 (b s, 2H), 3.59 (b s, 2H) 2.5 (bs, 2H, superimposed over DMSO signal). IR 3440, 3080-2710, 2588, 1599, 1583, 1512,1237, 702 cm-1. MS 373 (MH+ free base). Anal. Calc'd. for C25H28N2O·C2H2O4 : C, 70.11, H, 6.54, N, 6.06. Found: C, 70.65, H, 6.57, N, 6.19.

1. washwashed
2. temperatureis heated to 90° C. over the weekend
3. custom(~65 h) NMP is removed in vacuo at 100° C.
4. washThe solution is washed (H2 O)
5. customseparated
6. dry with materialdried (Na2SO4)
7. customevaporated in vacuo
8. customThe residue is purified by chromatography on silica using
9. temperatureincreasing proportion of MeOH in CH2Cl2 containing 0.5% Et3N
10. customTwo major products are isolated
11. washThe less polar one eluted with 4% MeOH / CH2Cl2 (0.5% Et3N) as an oil (0.19 g)
12. washThe more polar product (desired), is eluted with 10% MeOH/CH2Cl2
13. customobtained as an oil, 0.52 g (70%), which
14. customcrystallizes in to a waxy solid
15. customupon drying at 50° C. in vacuo
16. customdecomposing above 170° C