Methanol → Methyl 6-methylpiperidine-3-carboxylate

Methyl 6-methylnicotinate (4.9 g, 32.4 mmol) was combined with 10% Pd/C (wet, 2.5 g), methanol (40 mL) and acetic acid (50 mL) and hydrogenated at 40° C., (50 psi) for 15 hours. The mixture was filtered through a pad of Celite, washed with methanol, and concentrated under reduced pressure. The residue was co-evaporated with 80 mL of toluene and then with 50 mL of methanol. The residue was partitioned between 40 mL of dichloromethane and 20 mL of saturated K2CO3. The aqueous layer was extracted with dichloromethane and the combined organics dried with anhydrous K2CO3. The solution was concentrated and dried under vacuum to 5.0 g of pale yellow oil. The cis/trans product mixture was not well separated by TLC (Rf=0.55 and 0.57, CH2Cl2:MeOH:NH4OH, 90:9:1). The crude product mixture was taken directly to the next step.

1. filtrationThe mixture was filtered through a pad of Celite
2. washwashed with methanol
3. concentrationconcentrated under reduced pressure
4. customThe residue was partitioned between 40 mL of dichloromethane and 20 mL of saturated K2CO3
5. extractionThe aqueous layer was extracted with dichloromethane
6. dry with materialthe combined organics dried with anhydrous K2CO3
7. concentrationThe solution was concentrated
8. dry with materialdried under vacuum to 5.0 g of pale yellow oil
9. customThe cis/trans product mixture was not well separated by TLC (Rf=0.55 and 0.57, CH2Cl2:MeOH:NH4OH, 90:9:1)

ORD record

ord-88ff8f6b0c484a67a3b48d9008c052b5

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853219B2