反应详情

1,1-Dimethylethyl 4-[4-(2-fluoroethyl)-1-piperazinyl]-1-piperidinecarboxylate (10.2 g, 32.3 mmol) was dissolved in 40 mL of MeOH and 40 mL of 37% HCl. Reaction was stirred for 1 h, concentrated in vacuo and then a small amount of H2O was added back to solubilize the HCl salt of the product. When everything was in solution, solid K2CO3 was added to neutralize. The mixture was then concentrated in vacuo to remove H2O. Residue taken up in DCM and solids were filtered and washed with 20% MeOH/DCM. Filtrate was concentrated in vacuo and residue taken up in diethyl ether. Solids filtered and washed with diethyl ether several times. Combined filtrates were concentrated in vacuo to give desired product in two crops (2.42 g and 1.85 g) without further purification. Batches were combined together to give the title compound of step D (4.3 g, 68%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.40-4.58 (m, 2H), 3.15 (s, 1H), 2.91 (d, J=12.1 Hz, 2H), 2.35-2.59 (m, 12H), 2.15 (tt, J=11.36, 3.67 Hz, 1H), 1.63 (d, J=12.10 Hz, 2H), 1.19 (qd, J=11.85, 4.03 Hz, 2H).

1. customReaction
2. concentrationconcentrated in vacuo
3. additiona small amount of H2O was added back
4. additionwas added
5. concentrationThe mixture was then concentrated in vacuo
6. customto remove H2O
7. filtrationsolids were filtered
8. washwashed with 20% MeOH/DCM
9. concentrationFiltrate was concentrated in vacuo and residue
10. filtrationSolids filtered
11. washwashed with diethyl ether several times
12. concentrationCombined filtrates were concentrated in vacuo