反应详情

To 150 mg (0.42 mmol) 4-benzyloxy-1-[2-(1,2,3,4-tetrahydro-isoquinolin-7-yl)-ethyl]-1H-pyridin-2-one (example 24.2) in 5.0 mL THF is added 68 μL (0.83 mmol) aqueous 37% formaldehyde solution. The mixture is acidified with 3 drops of acetic acid and then 97 mg (0.46 mmol) sodium triacetoxy-borohydride is added. The reaction mixture is stirred 2 h at RT and additional 68 μL (0.83 mmol) aqueous 37% formaldehyde solution and 97 mg (0.46 mmol) sodium triacetoxy-borohydride are added. The reaction mixture is stirred overnight and additional 68 μL (0.83 mmol) aqueous 37% formaldehyde solution and 97 mg (0.46 mmol) sodium triacetoxy-borohydride is added and the reaction mixture is stirred additional 48 h at RT. The mixture is poured into aqueous 10% Na2CO3-solution, the layers are separated and the aqueous phase is extracted with DCM. The combined organic phase is washed a few times with water, dried over MgSO4, filtered and the solvent is evaporated. The residue is purified via reverse HPLC chromatography (Zorbax stable bond, C18; water (0.15% formic acid)/acetonitrile 95:5 to 5:95).

1. stirringThe reaction mixture is stirred overnight
2. stirringthe reaction mixture is stirred additional 48 h at RT
3. customthe layers are separated
4. extractionthe aqueous phase is extracted with DCM
5. washThe combined organic phase is washed a few times with water
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customthe solvent is evaporated
9. customThe residue is purified via reverse HPLC chromatography (Zorbax stable bond, C18; water (0.15% formic acid)/acetonitrile 95:5 to 5:95)