Hydrochloric Acid → rac-(2R,6S)-2,6-dimethylpiperidine-1-carbonyl chloride

Temperature

7.5 °C

To a solution of triphosgene (20.8 g, 70.0 mmol) in DCM (400 mL) at 5° C. was added pyridine (16.2 mL, 200 mmol) dropwise over 10 min, maintaining the temperature below 10° C. The solution was then stirred between 5-10° C. for 1 h, then cis-2,6-dimethyl piperidine (CAS: 766-17-6, 27.0 mL, 200 mmol) was added dropwise over 10 min and the resulting red solution stirred at RT for 4 days (reaction complete within <4 h). The solution was cooled to 3° C., then a pre-cooled (3° C.) 1M aqueous HCl solution (400 mL) was added and the mixture stirred at 5° C. for 30 min. The mixture was separated and the aqueous layer was extracted with DCM (200 mL), then the combined organic extracts passed through a hydrophobic fit and concentrated under vacuum affording Intermediate 3a as a red oil (31.5 g, 90%). 1H NMR (300 MHz, CDCl3): 1.30 (6H, d, J=7.09 Hz), 1.49-1.87 (6H, m), 4.46-4.56 (2H, m).

1. temperaturemaintaining the temperature below 10° C
2. stirringthe resulting red solution stirred at RT for 4 days
3. custom(reaction complete within <4 h)
4. temperatureThe solution was cooled to 3° C.
5. additionwas added
6. stirringthe mixture stirred at 5° C. for 30 min
7. customThe mixture was separated
8. extractionthe aqueous layer was extracted with DCM (200 mL)
9. concentrationconcentrated under vacuum

ORD record

ord-31b6b74ed33945b5a154b2b2259c25c5

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09359354B2