Reaktion #51612

Reaktionsgleichung

(−)-(R)-3,4-dihydro-2H-1-benzopyran-2-carbonyl chloride

magnesium oxide

1-(3-aminopropyl)-tetrahydro-2(1H)pyrimidinone

thiophene

thiophene

→

(R)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)-methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinone

Lösungsmittel

ethyl acetate

methanol

methanol

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationAfter uptake of H2 (1 eq.), the catalyst was filtered off
2. 2
   Sonstigethe filtrate was collected in a mixture of potassium acetate (7 g) in methanol (200 ml)
3. 3
   workup.ADDITIONwas added
4. 4
   Sonstige(16 hours at 25° C.; 16 hours at 50° C.)
5. 5
   FiltrationAfter uptake of hydrogen, the catalyst was filtered off
6. 6
   Sonstigethe filtrate was evaporated
7. 7
   workup.ADDITIONtreated with 50% NaOH
8. 8
   Extraktionextracted with DCM
9. 9
   SonstigeThe separated organic layer was dried
10. 10
    Filtrationfiltered
11. 11
    Sonstigethe solvent evaporated
12. 12
    SonstigeThe supernatant was decanted off
13. 13
    Sonstigethe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH NH3) 95/5)
14. 14
    SonstigeThe desired fractions were collected
15. 15
    Sonstigetheir solvent was evaporated

Vorschrift

A mixture of (−)-(R)-3,4-dihydro-2H-1-benzopyran-2-carbonyl chloride (0.2 mol) and magnesium oxide (40 g) in ethyl acetate (350 ml) was hydrogenated at 25° C. with palladium on activated carbon (10%) (5 g) as a catalyst in the presence of a solution (4%) of thiophene in methanol (5 ml). After uptake of H2 (1 eq.), the catalyst was filtered off and the filtrate was collected in a mixture of potassium acetate (7 g) in methanol (200 ml). A mixture of 1-(3-aminopropyl)-tetrahydro-2(1H)pyrimidinone (0.2 mol) in methanol (200 ml) was added and the mixture was hydrogenated (16 hours at 25° C.; 16 hours at 50° C.) with rhodium on activated carbon (5%, 3 g) as a catalyst in the presence of a solution (4%) of thiophene in methanol (3 ml). After uptake of hydrogen, the catalyst was filtered off and the filtrate was evaporated. The residue was stirred in water, treated with 50% NaOH, and extracted with DCM. The separated organic layer was dried, filtered and the solvent evaporated. The residue was stood overnight in 2-propanone (500 ml). The supernatant was decanted off and the residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH NH3) 95/5). The desired fractions were collected and their solvent was evaporated, yielding (R)-1-[3-[[(3,4-dihydro-2H-1-benzopyran-2-yl)-methyl]amino]propyl]tetrahydro-2(1H)-pyrimidinone (comp. 2).

Quelle