Formaldehyde → (2R)-1,2-dimethylpyrrolidine-2-carboxylic acid

To a parr flask containing 2-methyl-D-proline (432 mg, 3.34 mmol, 1.0 eq.), Formaldehyde 37 wt. % in water (1.0 mL, 37 mM, 11 eq.), 3.5 mL of methanol and 1 mL of water, Palladium 10 wt. % on Carbon (108 mg, 0.304 mmol, 0.304 eq.) was added. The flask was placed on a parr shaker and allowed to shake under 30 psi of hydrogen for -48 hours. Hydrogen was removed and reaction was washed through a pad of celite, which was subsequently washed with methanol. The organics where concentrated in vacuo and then azeotroped with toluene affording #152 (517 mg, 100%) as a solid. 1H NMR (400 MHz, methanol-d4): δ [3.61-3.56 (m, 1H), 3.07-2.96 (m, 1H), 2.68 (br s, 3H), 2.34-2.22 (m, 1H), 2.01-1.88 (m, 1H), 1.87-1.73 (m, 1H), 1.40 (br s, 3H)].

1. customHydrogen was removed
2. customreaction
3. washwas washed through a pad of celite, which
4. washwas subsequently washed with methanol
5. concentrationThe organics where concentrated in vacuo
6. customazeotroped with toluene affording #152 (517 mg, 100%) as a solid

ORD record

ord-23bb9c33dab441a7ba04ee587dedb15b

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08828401B2