Trifluoroacetic acid → 4-Morpholinopiperidine

To a stirred solution of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (Aldrich, 3.0 g, 15 mmol) in THF (25 mL), morpholine (Aldrich, 1.56 g, 18 mmol) and Ti(OiPr)4 (Aldrich, 5.58 mL) were added successively and the mixture was stirred at room temperature for 1 hour. Then, 15 mL of ethanol was added and followed by sodium cyanoborohydride (0.63 g, 10.05 mmol). The resulting mixture was stirred at room temperature over night and the reaction was quenched with addition of water (4 mL). The mixture was stirred for 30 minutes and the white solid was filtered out and the filtrate was evaporated. The residue was partitioned between ether and water and the organic layer was separated and dried with sodium sulfate. Removal of solvent gave a white solid which was treated with 40 mL of 50% TFA in methylene chloride. The solution was stirred at room temperature for 1 hour and the solvent was removed. The residue was lyophilized to give a white solid. 5.48 g, 98%. MS (m+H)+: 171.

1. stirringThe resulting mixture was stirred at room temperature over night
2. customthe reaction was quenched with addition of water (4 mL)
3. stirringThe mixture was stirred for 30 minutes
4. filtrationthe white solid was filtered out
5. customthe filtrate was evaporated
6. customThe residue was partitioned between ether and water
7. customthe organic layer was separated
8. dry with materialdried with sodium sulfate
9. customRemoval of solvent
10. customgave a white solid which
11. stirringThe solution was stirred at room temperature for 1 hour
12. customthe solvent was removed
13. customto give a white solid

ORD record

ord-fb13433e86294b4590b2bf02664e294d

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07211576B2