HCID 57040521, compound → HCID 57161946, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (±)-3-((αR*)-α-((2R*,5S*)-4-allyl-2,5-dimethyl-1-piperazinyl)-4-bromobenzyl)phenol (Example 2) (35.00 g, 0.0843 mol) in 400 mL anhydrous tetrahydrofuran was cooled to -78° C. n-Butyllithium (1.6M in hexane, 126 mL, 0.20 mol) was added dropwise. The reaction was stirred for 30 min. at -78° C. and then quenched with saturated ammonium chloride. After warming to room temperature, the reaction mixture was poured into 1000 mL ethyl acetate:1000 mL water. The ethyl acetate layer was washed with brine and dried over sodium sulfate. The solvent was removed to give 27.6 g of pink solid. The solid was recrystallized from ethyl acetate giving 19.4 g (68%) of (±)-3-((αR*)-α-((2R*,5S*)-4-allyl-2,5-dimethyl-1-piperazinyl)benzyl)phenol as a white solid, mp 172.5°-175.5° C. NMR (200 MHz, DMSO-d6): δ 0.96 (d, J=6 Hz, 3H); 1.08 (d, J=6 Hz, 3H); 1.85 (t, J=11 Hz, 1H); 2.09 (t, J=11 Hz, 1H); 2.5-2.9 (m, 5H); 3.15 (dd, J=5.4 Hz and 15, 1H); 4.9 (s, 1H); 5.1-5.2 (2d, 2H); 5.7-5.9 (m, 1H); 6.55 (d, J=8 Hz, 1H); 6.8 (d, J=8 Hz, 1H); 6.85 (s, 1H); 7.07 (t, J=8 Hz, 1H); 7.2-7.4 (m, 5H); 9.3 (s, 1H). The free amine was dissolved in ethanol and converted to the monohydrochloride salt by titration to pH of 3.8 with ethanolic hydrogen chloride. The salt was precipitated from ethanol with diethyl ether to give 15.82 g as a white solid. Calc. for C22 H28N2O HCl 0.5 H2O: C, 69.18; H, 7.92; N, 7.33; Cl, 9.28. Found: C, 69.55; H, 8.03; N, 7.31; Cl, 9.27.

Provenance & Evidence