تفاعل #2182585

معادلة التفاعل

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

CF3COOH

→

amine

المردود 70.1%

3-[3 (S)-[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 (310 mg) was purified by preparative HPLC (column
3. 3
   workup.WAIT40-50% B in A in 6 min
4. 4
   workup.WAIT50-100% in 1 min
5. 5
   workup.WAITback to 40% in 1 min)
6. 6
   أخرىThe eluate was partially evaporated under reduced pressure (bath 30° C.)
7. 7
   أخرىto remove CH3OH
8. 8
   غسيلThe residue was washed with saturated aqueous NaHCO3 solution
9. 9
   استخلاصextracted with EtOAc
10. 10
    غسيلThe combined organic layers were washed with brine
11. 11
    أخرىdried
12. 12
    تركيزAfter concentrated in vacuo

الإجراء التجريبي

To a 25 mL round-bottom flask containing a solution of 3-[3(S)-[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 (310 mg) was purified by preparative HPLC (column: SunFire Prep C18, 150×19 mm, 5 μm particle size; UV detection at 270 nm; flow 20 mL/min; mobile phase: A, water with 0.05% CF3COOH; B, methanol; 40-50% B in A in 6 min, 50-100% in 1 min, back to 40% in 1 min). The eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3OH. The residue was washed with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried. After concentrated in vacuo, the free amine (280 mg, 70%) was obtained as light-yellow solid. 1H NMR (CDCl3, 300 MHz) δ 7.66 (s, 1H), 7.61 (s, 1H), 7.37-7.30 (m, 5H), 6.34 (s, 1H), 4.54 (s, 2H), 4.01-3.94 (m, 2H), 3.54-3.49 (m, 3H), 3.48-3.22 (m, 3H), 3.12-3.00 (m, 2H), 2.91 (t, 1H , J=9.6 Hz), 2.36-2.23 (m, 1H), 2.21-2.10 (m, 1H), 2.06-1.79 (m, 3H), 1.76-1.50 (m, 6H). LC-MS (ESI) m/z 396 (M+H+).

المصدر