反应详情

TFA (2.5 mL, 3.7 g, 32 mmol) was added dropwise to a solution of 1-(t-butoxycarbonyl)-4-(3,3-difluoro-3-phenylpropyl)piperidine (42 mg, 0.12 mmol, from EXAMPLE 154, Step C) in CH2Cl2 (2.5 mL) at 0° C. After 80 min., the solution was transferred using a double-ended needle to a rapidly stirred solution of NaHCO3 (5.0 g, 60 mmol) in H2O (50 mL). Ether (50 mL) and 2.5 N NaOH (20 mL) were added, followed by solid NaCl to saturate the aqueous layer. The aqueous layer was separated and extracted with ether (50 mL). The organic layers were washed in succession with saturated aq. NaCl (20 mL), combined, dried (Na2SO4), decanted,and evaporated to give the title compound as 27 mg of colorless oil. 1H NMR (400 MHz, CD3OD) δ 7.51-7.40 (m, 5H), 2.98 (dm, J=12,22H), 2.53 (td, J=12, 3, 2H), 2.24-2.10 (m, 2H), 1.65 (bd, J=12, 2H), 1.42-1.26 (m, 3H), 1.06 (qd, J=12,4,2H); ESI-MS 240 (M+H); HPLC A: 2.25 min.

1. concentrationto saturate the aqueous layer
2. customThe aqueous layer was separated
3. extractionextracted with ether (50 mL)
4. washThe organic layers were washed in succession with saturated aq. NaCl (20 mL)
5. dry with materialdried (Na2SO4)
6. customevaporated