反应详情

温度

35 °C

The free base of methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (0.28 g, 0.53 mmol) and L-tartaric acid (84.4 mg, 0.56 mmol, 99.5%) were dissolved in ethanol (5 mL) to give a clear solution. The solvent was removed in vacuo to dryness, and the residue was redissolved in 95% ethanol:MeCN (3:97 v/v) (10.5 mL) at 35° C. A seed crystal was added and the resulting solution was stirred at 35° C. for 2 hr, then cooled to rt slowly, and stirred for 48 hr. The resulting white crystal was filtered and washed with MeCN (2×5 mL) to give 1:1 L-tartrate of methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(methylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (0.31 g, 84%). Selected 1H NMR (CD3OD, 400 MHz), δ: 7.36 (m, 3H), 7.22 (d, 1H), 4.40 (s, 2H), 4.18-4.00 (m, 3H), 3.86 (m, 3H), 3.62 (s, 3H), 3.40 (m, 1H), 3.24 (m, 3H), 3.18-2.84 (m, 5H), 2.72 (s, 3H), 1.90-1.08 (m, 12H); mp=122-127° C. MS ESI +ve m/z 525 (M+1).

1. customto give a clear solution
2. customThe solvent was removed in vacuo to dryness
3. dissolutionthe residue was redissolved in 95% ethanol:MeCN (3:97 v/v) (10.5 mL) at 35° C
4. additionA seed crystal was added
5. temperaturecooled to rt slowly
6. stirringstirred for 48 hr
7. filtrationThe resulting white crystal was filtered
8. washwashed with MeCN (2×5 mL)