反应详情

To a suspension of manganese dioxide (15.5 g, 178 mmol) in DCM (100 mL) was added 5-hydroxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester (3.35 g, 11.8 mmol) and after 6 h stirring at RT a further addition of manganese dioxide (5 g, 57 mmol) was made. After a further 1 h stirring at RT Celite (7 g) was added and the solution was filtered through a bed of Celite™ giving a clear pale yellow solution. The Celite™ was washed with DCM and the volume of the combined organic solution adjusted to 100 mL by evaporation. N-Methylpiperazine (1.31 mL, 11.8 mmol) and acetic acid (0.68 mL) were added followed by sodium triacetoxyborohydride (4.98 g, 23.5 mmol). The yellow solution was stirred 16 h giving a colourless solution. To the solution was added 2M-HCl (10 mL, 20 mmol) giving an effervescence. After 30 min water (10 mL) and K2CO3 (5.5 g, 39.8 mmol) were added and the organic phase was dried (Na2SO4). After filtration 4M−HCl in dioxan (6 mL) was added with stirring and the suspension was evaporated to dryness. The residue was dissolved in MeOH with warming and after evaporation the solid was washed on a sinter with EtOAc then petrol (bp 40-60° C.) followed by drying in vacuo at 50° C. to give the title compound 3.61 g (70%). 1H NMR (400 MHz, Me-d3-OD): 7.65-7.51 (2H, m), 7.51-7.27 (6H, m), 5.23 (2H, s), 4.83-4.69 (4H, m), 4.49 (2H, s), 3.66 (8H, d), 3.03 (3H, s)

1. stirringAfter a further 1 h stirring at RT Celite (7 g)
2. additionwas added
3. filtrationthe solution was filtered through a bed of Celite™
4. customgiving a clear pale yellow solution
5. washThe Celite™ was washed with DCM
6. customthe volume of the combined organic solution adjusted to 100 mL by evaporation
7. stirringThe yellow solution was stirred 16 h
8. customgiving a colourless solution
9. customgiving an effervescence
10. dry with materialthe organic phase was dried (Na2SO4)
11. filtrationAfter filtration 4M−HCl in dioxan (6 mL)
12. additionwas added
13. stirringwith stirring
14. customthe suspension was evaporated to dryness
15. dissolutionThe residue was dissolved in MeOH
16. temperaturewith warming
17. customafter evaporation the solid
18. washwas washed on a sinter with EtOAc
19. customby drying in vacuo at 50° C.