Reaktion #598871

Reaktionsgleichung

MeCHO

benzyl 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)amino)cyclobutyl)propanoate

NaBH3CN

AcOH

→

Benzyl 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(ethyl)amino)cyclobutyl)propanoate

Ausbeute 66.0%

Lösungsmittel

MeOH

Water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenthe mixture was concentrated in vacuo
2. 2
   ExtraktionThen, the mixture was extracted with DCM (30 mL×3)
3. 3
   WaschenThe combined organic phase was washed with brine
4. 4
   Trocknendried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated
7. 7
   SonstigeThe crude was purified by SGC (DCM: MeOH=100:1-20:1)
8. 8
   Sonstigeto obtain the target (2.6 g, yield: 66%) as a white solid

Vorschrift

To a mixture of benzyl 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)amino)cyclobutyl)propanoate (3.76 g, 7.2 mmol) and NaBH3CN (5.9 g, 93.6 mmol) in MeOH (40 mL) was added AcOH to adjust to pH=6. Then, 40% MeCHO (8.7 mL, 122.5 mmol) was added and the mixture was stirred at 30° C. for 1.5 h. Water (15 mL) was added and the mixture was concentrated in vacuo. Then, the mixture was extracted with DCM (30 mL×3). The combined organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The crude was purified by SGC (DCM: MeOH=100:1-20:1) to obtain the target (2.6 g, yield: 66%) as a white solid. 1H NMR (500 MHz, MeOD): δH 8.26 (s, 1H), 8.23 (m, 1H), 7.37-7.28 (m, 5H), 6.24 (s, 1H), 5.52-5.49 (m, 1H), 5.10-5.06 (m, 3H), 4.41-4.40 (m, 1H), 3.20-2.90 (m, 2H), 2.80-2.60 (m, 2H), 2.12-1.77 (m, 4H), 1.74-1.60 (m, 3H), 1.39 (s, 3H), 1.26-1.22 (m, 3H), 0.94-0.89 (m, 3H) ppm; ESI-MS (m/z): 551.3 [M+1]+.

Quelle