Dimethylformamide → tert-butyl (2R,6S)-2-formyl-6-methylpiperidine-1-carboxylate

Temperature

-20 °C

A solution of N-Boc-2-Methyl-Piperidine (9.4 g, 46.9 mmol) in 94 mL of ether was cooled to −60° C. and treated with TMEDA (7.1 mL, 46.9 mmol) followed by sec-BuLi (49.2 mL, 51.66 mmol) dropwise. The mixture was slowly warmed to −20° C. and stirred for 30 min and then cooled to −78° C. The mixture was treated with a solution of DMF (5.5 mL, 70.44 mmol) in 16 mL of ether via syringe, stirred for 10 min, and then quenched with 75 mL saturated ammonium chloride solution. The mixture was warmed to room temperature, and the organic layer was separated. The aqueous layer was extracted with ether, and the combined extracts were dried over K2CO3. The organic layer was concentrated to give a crude product as an oil which was chromatographed on silica with hexanes:EtOAc (4:1) to afford 6.5 g (66%) of the trans isomer and 2.1 g (21%) of the cis isomer. Both products were homogeneous by TLC analysis, with the cis isomer positiioned just above the trans isomer. 1H NMR (250 MHz) δ 9.28-9.26 (d, 1H), 4.25 (br. d, 1H), 3.64-3.57 (m, 1H), 1.74-1.46 (m, 15H), 1.09-1.04 (d, 3H); 13C NMR (62.7 MHz) 196.3 (s), 155.1 (s), 77.4 (s), 59.2 (s), 47.3 (s), 29.3 (s), 28.2 (s), 25.4 (s), 16.3 (s) ppm.

1. temperaturecooled to −78° C
2. stirringstirred for 10 min
3. customquenched with 75 mL saturated ammonium chloride solution
4. temperatureThe mixture was warmed to room temperature
5. customthe organic layer was separated
6. extractionThe aqueous layer was extracted with ether
7. dry with materialthe combined extracts were dried over K2CO3
8. concentrationThe organic layer was concentrated

ORD record

ord-e09f393172034c62af82b5c75e003caa

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168657B2