Hydrochloric Acid → HCID 22661402, compound

3-Amino-4,4,4-trifluorobutyric acid (10 g, 63.7 mmol) was added to a solution of sodium hydrogen carbonate (6.95 g, 82.8 mmol) in water (100 mL). A solution of 1-[[(9H-fluoren-9-ylmethoxy)carbonyl]oxy-2,5-pyrrolidinedione (Fmoc-OSu; 25.78 g, 76.4 mmol) in tetrahydrofuran (200 mL) was added. The solution was stirred at room temperature for 19 h and then acidified to pH 1 with 3 M HCl (250 mL). The mixture was extracted with ethyl acetate (250 mL then 100 mL) and the combined organic layers were washed with saturated brine (3×100 mL), dried (Na2SO4), filtered and concentrated to approximately 200 mL. Crystallization occurred on concentration. The mixture was allowed to stand for 10 min, then the solid was filtered off, washed with ethyl acetate and dried in a vacuum oven at 50° C. to give 3-[N-[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4,4,4-trifluorobutyric acid (11.47 g) as a white solid, mp 187-189° C. The mother liquor was concentrated to 80 mL. Crystallization occurred on concentration. The solid was filtered off, washed with ethyl acetate and dried in a vacuum oven at 50° C. to give a second batch of product (4.69 g). The overall yield was16.16 g (67%).

1. extractionThe mixture was extracted with ethyl acetate (250 mL
2. wash100 mL) and the combined organic layers were washed with saturated brine (3×100 mL)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated to approximately 200 mL
6. customCrystallization
7. concentrationoccurred on concentration
8. waitto stand for 10 min
9. filtrationthe solid was filtered off
10. washwashed with ethyl acetate
11. customdried in a vacuum oven at 50° C.

ORD record

ord-d33d0891e78646d4816dd6e5e60d47ef

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06331640B1