Reaktion #355919

Reaktionsgleichung

pentachlorophenyl 4-(3-piperdin-1-ylpropoxy)benzoate

Pentachlorophenyl 4-(3-piperidin-1-ylpropoxy)benzoate

N-benzyl-4-fluoroisoindoline

N-Benzyl-4-fluoroisoindoline

→

title compound ( E55 )

Ausbeute 17.6%

N-[4-(3-Piperidin-1-ylpropoxy)benzoyl]-4-fluoroisoindoline hydrochloride

Ausbeute 17.6%

Lösungsmittel

IPA

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe mixture was filtered
2. 2
   Sonstigeevaporated
3. 3
   workup.DISSOLUTIONThe residue was redissolved in EtOAc (20 ml)
4. 4
   Waschenwashed with saturated sodium hydrogen carbonate solution (10 ml), water (2×10 ml), brine (10 ml)
5. 5
   Trocknendried (MgSO4)
6. 6
   Sonstigeevaporated
7. 7
   SonstigeThe residue was chromatographed on a silica gel flash column [step gradient 2-8% MeOH (containing 10% 0.880 ammonia solution) in DCM]
8. 8
   SonstigeThe required fractions were evaporated
9. 9
   workup.DISSOLUTIONredissolved in DCM
10. 10
    workup.ADDITIONtreated with excess 4M HCl in dioxan

Vorschrift

A mixture of pentachlorophenyl 4-(3-piperdin-1-ylpropoxy)benzoate (D10) (500 mg) and N-benzyl-4-fluoroisoindoline (D9) (200 mg) in IPA (10 ml) at rt was treated with poly(methylhydrosiloxane) (0.16 ml) and palladium hydroxide on carbon (30 mg, 20% Pd) and stirred overnight. The mixture was filtered and evaporated. The residue was redissolved in EtOAc (20 ml), washed with saturated sodium hydrogen carbonate solution (10 ml), water (2×10 ml), brine (10 ml), dried (MgSO4) and evaporated. The residue was chromatographed on a silica gel flash column [step gradient 2-8% MeOH (containing 10% 0.880 ammonia solution) in DCM]. The required fractions were evaporated, then redissolved in DCM and treated with excess 4M HCl in dioxan. The title compound (E55) (65 mg) was obtained by crystallisation from acetone. MS electrospray (+ion) 383 (MH+). 1H NMR δ (DMSO-d6): 10.15 (1H, m), 7.09-7.65 (7H, m),4.89 (4H, m), 4.13 (2H, t, J=6 Hz), 3.46 (2H, m), 3.16 (2H, m), 2.90 (2H, m), 2.22 (2H, m), 1.79 (5H, m), 1.42 (1H, m).

Quelle