反应详情

4-Fluoro-N-ethylaniline [NMR (200 MHz, DMSO-d6): δ1.25 (t, J=7.1 Hz, 3H); 3.12 (q, J=7.1 Hz, 2H); 3.24 (br s, 1H); 6.57 (dd, J1 =4.5 Hz, J2 =9.0 Hz, 2H); 6.90 (t, J=8.9 Hz, 2H)] was prepared from 4-fluoroaniline and acetic anhydride, coupled with 3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-(tert-butyldimethylsilyloxy)benzyl)benzoyl chloride, deprotected and purified by the methods described in Example 10 to give (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-ethyl-N-(4-fluorophenyl)benzamide as an off-white powder. NMR (200 MHz, DMSO-d6): δ0.91 (d, J=6.1 Hz, 3H); 0.98 (d, J=6.0 Hz, 3H); 1.08 (t, J=7.0 Hz, 3H); 1.71 (dd, J1 =7.0 Hz, J2 =11.3 Hz, 1H); 2.05 (dd, J1 =7.2 Hz, J2 =10.8 Hz, 1H); 2.31 (d, J=11.4 Hz, 1H) 2.36-2.57 (m, 2H); 2.69 (dd, J1 =2.2 Hz, J2 =10.7 Hz, 1H); 2.85 (dd, J1 =7.0 Hz, J2 =13.9 Hz, 1H); 3.18 (dd, J1 =5.3 Hz, J2 =13.9 Hz, 1H); 3.84 (q, J=7.0 Hz, 2H); 4.78 (s, 1H); 5.11 (d, J=10.0 Hz, 1H); 5.18 (d, J=16.4 Hz, 1H); 5.65-5.88 (m, 1H); 6.46 (d, J=7.4 Hz, 1H); 6.58 (s, 1H); 6.65 (d, J=8.1 Hz, 1H); 7.01-7.27 (m, 9H); 9.33 (s, 1H). Mass spectrum (CI--CH4) m/e: 502 (M+1.90%), 348 (15%), 153 (100%). [α]D20 =6.30° (abs. ethanol, c=1.1) The free amine (0.313 g) was dissolved in ethanol and titrated with ethanolic hydrogen chloride to pH 3.95 followed by precipitation with diethyl ether from dichloromethane to give 0.263 g of the monohydrochloride salt as a hygroscopic white powder. Calc. for C31H36N3O2F HCl H2O: C, 66.95; H, 7.07; N, 7.56; Cl, 6.38. Found: C, 66.97; H, 7.10; N, 7.47; Cl, 6.41.

1. custompurified by the methods