تفاعل #2182579

معادلة التفاعل

3-[3(R)-[3-(benzyloxy)propyl]-1-pyrrolidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine

CF3COOH

→

base

المردود 70.1%

3-[3(R)-[3-(Benzyloxy)propyl]-1-pyrrolidinyl]-5-[(2(S)-pyrrolidinyl)methoxy]pyridine

المردود 70.1%

المذيبات

CH2Cl2 H2O

ظروف التفاعل

المعالجة

1. 1
   أخرىAfter evaporation under reduced pressure
2. 2
   أخرىthe crude product (500 mg) was purified by preparative HPLC (column
3. 3
   workup.WAIT40-100% of B in A in 8 min
4. 4
   workup.WAITback to 40% in 1 min)
5. 5
   أخرىThe eluate was partially evaporated under reduced pressure (bath 30° C.)
6. 6
   أخرىto remove CH3OH
7. 7
   استخلاصextracted with EtOAc
8. 8
   غسيلThe combined organic layers were washed with brine
9. 9
   تجفيفdried over Na2SO4
10. 10
    تركيزAfter concentration in vacuo

الإجراء التجريبي

To a 25 mL round-bottom flask containing a solution of 3-[3(R)-[3-(benzyloxy)propyl]-1-pyrrolidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (500 mg, 1.01 mmol) in CH2Cl2/H2O (7.5/0.15 mL) was added CF3COOH (1.5 mL) at 0° C. under N2. The reaction mixture was stirred for 3 h at room temperature. After evaporation under reduced pressure, the crude product (500 mg) was purified by preparative HPLC (column: SunFire Prep C18, 150×19 mm, 5 μm particle size; UV detection at 220 and 254 nm; flow 20 mL/min; mobile phase: A, water with 0.05% CF3COOH; B, methanol; 40-100% of B in A in 8 min, back to 40% in 1 min). The eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3OH. The residue was basified with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. After concentration in vacuo, the free base (280 mg, 70%) was obtained as a light-yellow solid. 1H NMR (CDCl3, 300 MHz) δ 7.65 (s, 1H), 7.61 (s, 1H), 7.37-7.33 (m, 5H), 6.33 (s, 1H), 4.54 (s, 2H), 4.01-3.97 (m, 2H), 3.69-3.59 (m, 1H), 3.53 (t, J=6.3 Hz, 2H), 3.50-3.20 (m, 4H), 3.09-3.06 (m, 2H), 2.90 (t, 1H, J=6.3 Hz), 2.38-2.10 (m, 2H), 2.03-1.83 (m, 3H), 1.79-1.51 (m, 5H). LC-MS (ESI) m/z 396 (M+H+).

المصدر