Formaldehyde → HCID 118431255, compound

To a solution of (2R,4R)-4-methylpiperidine-2-carboxylic acid (2 g, 13.97 mmol) in MeOH (40 mL) and water (40.0 mL) was added paraformaldehyde (2.52 g, 27.94 mmol) and Pd/C (10%) (0.8 g, 7.52 mmol). The reaction mixture was stirred under a hydrogen atmosphere at room temperature overnight. From TLC, the reaction was not completed. Another one equivalent of paraformaldehyde (2.52 g, 27.94 mmol) was added and the reaction mixture was stirred another 24 hours. TLC indicated the reaction was completed and reaction mixture was filtered, washed the catalyst with MeOH (2×30 mL). The filtrate was concentrated in vacuo to give crude product as a white solid, which was washed with ether (3×30 mL), dried in high vacuum overnight to yield (2R,4R)-1,4-dimethylpiperidine-2-carboxylic acid (1) (1.870 g, 85%) as a white solid. LC-MS: 158 (M+1); 1H NMR (400 MHz, D2O) δ ppm 0.97 (d, J=5.52 Hz, 3H), 1.54 (br. s, 1H), 1.71-1.87 (m, 3H), 1.91-2.07 (m, 1H), 2.84 (s, 3H), 3.13 (td, J=8.41, 3.76 Hz, 1H), 3.35 (m, 1H), 3.65 (m, 1H).

1. stirringthe reaction mixture was stirred another 24 hours
2. customreaction mixture
3. filtrationwas filtered
4. washwashed the catalyst with MeOH (2×30 mL)
5. concentrationThe filtrate was concentrated in vacuo
6. customto give crude product as a white solid, which
7. washwas washed with ether (3×30 mL)
8. customdried in high vacuum overnight

ORD record

ord-31ca199585bc4e95bf922690b9195ce7

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09427479B2