Acetic Anhydride → 1-(9-Fluorenylmethyl)piperidine

In a 10 mL-syringe equipped with a polypropylene disk are introduced 1.5 g of aminomethylpolystyrene (Sigma, 0.81 mmol NH2 /g of resin), 44.6 mg (0.24 equiv.) of 1-hydroxybenzotriazole in 0.8 mL of DMF, 63.2 mg (0.24 equiv.) of DCC in 2 mL of DCM and 103 mg (0.24 equiv.) of N-Fmoc-6-aminohexanoic acid in 5 mL of DCM and 0.4 mL of DMF and left to react, with occasional stirring, for two hours. The resin is washed with DMF (3×1 min), DCM (3×1 min) and MeOH (3×1 min), dried and the functionalization is determined on an aliquot. The remaining amine groups are acetylated with acetic anhydride (100 equiv.) in DMF for 10 min, after which time DIEA (10 equiv.) is added and left to react for 10 min more, and the resin is washed again. The absence of free amine groups is confirmed by the ninhydrin test. In order to eliminate the Fmoc group, and at the same time determine the degree of substitution, the resin is treated with a solution of 50% piperidine in DMF (3×2 min) and washed with DCM (3×1 min), DMF and MeOH. The filtrates from the treatment with piperidine and DCM washes are pooled and the amount of N-(9-fluorenylmethyl)piperidine formed in the deprotection determined spectrophotometrically (lambda=300 nm, epsilon=7800). Resins with a substitution degree between 0.05 and 0.1 mmol NH2 /g resin are obtained.

1. customto react, with occasional stirring, for two hours
2. washThe resin is washed with DMF (3×1 min), DCM (3×1 min) and MeOH (3×1 min)
3. customdried
4. waitleft
5. customto react for 10 min more
6. washthe resin is washed again
7. additionthe resin is treated with a solution of 50% piperidine in DMF (3×2 min)
8. washwashed with DCM (3×1 min), DMF and MeOH

ORD-Eintrag

ord-c4a90ac8d183432ca48f709d0e4e8314

Quelldatensatz

uspto-grants-2000_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06153742