反应详情

To a mixture of (R)-N,N-diisopropyl-3-(2-benzyloxy-5-bromophenyl)-3-phenylpropanamine (10.00 g, 20.81 mmol) (prepared as described in WO 94/11337, Example 1) and Mg (1.57 g, 64.52 mmol) in THF (50 mL) was added 1,2-dibromoethane (3.59 mL, 41.63 mmol) and the solution was self-refluxing for a while. The mixture was refluxed for 1 h whereafter the solution was cooled and tosyl azide (4.10 g, 20.81 mmol) in diethyl ether (100 mL) was added with constant stirring while keeping the temperature at 0° C. wherafter the temperature was allowed to rise to room temperature for 4 h. A solution of tetra-sodium pyrophosphate decahydrate (4.46 g, 10.00 mmol) in 50 mL water was added. A precipitate was filtered off and the filtrate was evaporated. The residue was extracted with diethyl ether, the organic phase was dried (MgSO4) and evaporated. The residue was chromatographed on silica (n-hexane-ethanol, 8:2). The product was crystallised from ethanol to give 1.15 g (13%); IR (KBr) 2116 (N3) cm−1; 1H NMR (CDCl3) δ0.92 (d, 12H), 2.10 (m, 2H), 2.33 (m, 2H), 2.95 (m, 2H), 4.40 (t, 1H), 5.00 (s, 2H), 6.81 (d, 2H), 6.97 (s, 1H), 7.10-7.40 (m, 10H).

1. temperaturethe solution was self-refluxing for a while
2. temperatureThe mixture was refluxed for 1 h whereafter the solution
3. temperaturewas cooled
4. customat 0° C.
5. filtrationA precipitate was filtered off
6. customthe filtrate was evaporated
7. extractionThe residue was extracted with diethyl ether
8. dry with materialthe organic phase was dried (MgSO4)
9. customevaporated
10. customThe residue was chromatographed on silica (n-hexane-ethanol, 8:2)
11. customThe product was crystallised from ethanol
12. customto give 1.15 g (13%)