Tetrahydrofuran → HCID 117966661, compound

Temperature

-45 °C

A solution of (R)-1-tert-butyl 2-ethyl 6-oxopiperidine-1,2-dicarboxylate (D19) (0.5 g, 1.84 mmol) in toluene (5 ml) was cooled at −50° C. LiEt3BH 1M solution in THF (1.93 ml, 1.93 mmol) was added dropwise in a manner that the reaction temperature did not exceed −45° C. After complete addition the mixture was stirred at −45° C. for 30 minutes. DIPEA (1.38 ml, 7.92 mmol) was added to the reaction maintaining the temperature below −45° C. followed by the addition of DMAP (3.4 mg, 0.027 mmol). The reaction mixture was then charged with TFAA (0.3 ml, 2.11 mmol) keeping the temperature below −45° C. After complete addition, the reaction mixture was warmed to 20-25° C. within one hour and kept for an additional 4 hrs at this temperature. Reaction mixture was quenched by slow addition of water. Phases were separated and the organics washed with water, dried over Na2SO4 and concentrated to obtain a clear oil, which was used as such to be subjected to the same procedure once again to afford the title compound (D20) (260 mg).

1. customdid not exceed −45° C
2. additionAfter complete addition the mixture
3. temperaturemaintaining the temperature below −45° C.
4. customthe temperature below −45° C
5. additionAfter complete addition
6. temperaturethe reaction mixture was warmed to 20-25° C. within one hour
7. waitkept for an additional 4 hrs at this temperature
8. customReaction mixture
9. customwas quenched by slow addition of water
10. customPhases were separated
11. washthe organics washed with water
12. dry with materialdried over Na2SO4
13. concentrationconcentrated
14. customto obtain a clear oil, which

ORD record

ord-439e056941d04249b8ef0025279220ad

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181279B2