반응 #51612

반응 방정식

(−)-(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

용매

ethyl acetate

methanol

methanol

methanol

반응 조건

후처리

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

실험 절차

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).

출처