Hydrochloric Acid → 1-{[(9H-Fluoren-9-yl)methoxy]carbonyl}piperidine-4-carboxylic acid

Piperidine-4-carboxylic acid (15.00 g, 116 mmol) was added to a solution of sodium hydrogen carbonate (12.7 g, 151 mmol) in water (200 mL) and the mixture was stirred for 10 min. A solution of 1-[[(9H-fluoren-9-ylmethoxy)carbonyl]oxy-2,5-pyrrolidinedione (Fmoc-OSu; 46.9 g, 139 mmol) in tetrahydrofuran (400 mL) was added. The solution was stirred at room temperature for 20 h and then acidified to pH 1 with 3 M HCl (500 mL). The mixture was extracted with ethyl acetate (200 mL then 100 mL) and the combined organic layers were washed with saturated brine (3×100 mL), dried (Na2SO4), filtered and concentrated to approximately 100 mL. Crystallization occurred on concentration. The mixture was allowed to stand for 2 h, then the solid was filtered off, washed with ethyl acetate and dried in a vacuum oven at 60° C. to give N-[(9H-fluoren-9-ylmethoxy)carbonyl]piperidine-4-carboxylic acid (34.51 g, 85%) as a white solid, mp 187-189° C.

1. stirringThe solution was stirred at room temperature for 20 h
2. extractionThe mixture was extracted with ethyl acetate (200 mL
3. wash100 mL) and the combined organic layers were washed with saturated brine (3×100 mL)
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated to approximately 100 mL
7. customCrystallization
8. concentrationoccurred on concentration
9. waitto stand for 2 h
10. filtrationthe solid was filtered off
11. washwashed with ethyl acetate
12. customdried in a vacuum oven at 60° C.

ORD record

ord-304ea2a7b36243989b19f182971c73dd

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06803384B2