تفاعل #2182619

معادلة التفاعل

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

CF3COOH

water

→

base

المردود 67.7%

3-[3(R)-[(3-Phenylpropoxy)methyl]-1-pyrrolidinyl]-5-[(2(S)-pyrrolidinyl)methoxy]pyridine

المردود 67.7%

المذيبات

CH2Cl2

ظروف التفاعل

المعالجة

1. 1
   تركيزAfter concentration under vacuum
2. 2
   أخرىthe crude product was purified by preparative HPLC (column
3. 3
   أخرى0-6 min, 40% to 50% B
4. 4
   أخرى6-7 min, 50%
5. 5
   أخرى7-8 min, 100%
6. 6
   أخرىThe eluate was partially evaporated under reduced pressure (bath 30° C.)
7. 7
   أخرىto remove CH3OH
8. 8
   استخلاصextracted with EtOAc
9. 9
   غسيلThe combined organic layers were washed with brine
10. 10
    أخرىdried
11. 11
    تركيزAfter concentration in vacuo

الإجراء التجريبي

To a solution of 3-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-[3(R)-[(3-phenylpropoxy)methyl]-1-pyrrolidinyl]pyridine (280 mg, 0.56 mmol) in CH2Cl2 (5 mL) was added a mixture of CF3COOH (1 mL) and water (0.1 mL) under N2. The solution was stirred overnight at room temperature. After concentration under vacuum, the crude product 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% TFA; B, MeOH; 0-6 min, 40% to 50% B in A; 6-7 min, 50%; 7-8 min, 100%). 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. After concentration in vacuo, the free base (150 mg, 67%) was obtained as a yellowish oil. 1H NMR (CDCl3, 300 MHz) δ 7.67 (d, 1H, J=2.1 Hz), 7.64 (d, 1H, J=2.1 Hz), 7.32-7.19 (m, 5H), 6.37 (t, 1H, J=2.1 Hz), 4.03-3.96 (m, 2H), 3.64-3.60 (m, 1H), 3.49-3.29 (m, 7H), 3.13-3.01 (m, 3H), 2.90 (br s, 1H), 2.74-2.63 (m, 3H), 2.19-2.13 (m, 1H), 2.04-1.88 (m, 6H), 1.69-1.57(m, 1H). LC-MS (ESI) m/z 396 (M+H+).

المصدر