tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 60108792, compound

Temperature

-78 °C

To a solution of 7-bromoindole (400 mg, 2.04 mmol) in THF (20 mL) under an argon atmosphere and cooled to −78° C. was added n-butyllithium (3.1 mL, 2.0M, 6.1 mmol) dropwise. The reaction was stirred at −78° C. for 15 minutes then warmed to 5° C. and maintained for 30 minutes. The reaction was cooled back to −78° C. and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (813 mg, 4.08 mmol) was added dropwise in THF (5 mL). The reaction was allowed to come to room temperature and stirred for 1 h. The reaction was quenched with water (15 mL) and extracted with EtOAc (3×20 mL). The combined acetate layers were washed with brine, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo and chromatographed on silica eluting with 20% acetone in hexanes to afford 4-hydroxy-4-(1H-indol-7-yl)-piperidine-1-carboxylic acid tert-butyl ester as a white foam (520 mg).

1. temperaturethen warmed to 5° C.
2. temperaturemaintained for 30 minutes
3. temperatureThe reaction was cooled back to −78° C.
4. customto come to room temperature
5. stirringstirred for 1 h
6. customThe reaction was quenched with water (15 mL)
7. extractionextracted with EtOAc (3×20 mL)
8. washThe combined acetate layers were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationThe filtrate was concentrated in vacuo
12. customchromatographed on silica eluting with 20% acetone in hexanes

ORD record

ord-8e9465deba944b9b8e6b90d40d342d1f

Source dataset

uspto-grants-2004_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06787535B2