4,4-diMethyl-Proline synthesis

Yield:-

Reaction Conditions:

with barium dihydroxide in water at 150; for 6 h;

Steps:

26.3

Step 3: 4, 4-Dimethylpyrrolidine-2-carboxylic acid; A suspension of 20.4 g (0.13 mol) of 3-chloro-5, 5-dimethyl-2-piperidone and 45.2 g (0.14 mol) of Ba (OH) 3-8H20 in 252 mL of water was heated in a Parr apparatus at 150 °C for 6 h. Then, 18.6 g (0.14 mol) of ammonium sulphate were added. The precipitate was filtered off, and the solution was concentrated under reduced pressure to dryness. Crude 4, 4-dimethylpyrrolidine-2-carboxylic acid was obtained as a white solid (37.5 g). (J. Med. Chem. , 20,1176 (1977), EP 0 447 704 A1, page 17) 'H NMR (D20) 8 1. 10 (s, 3H), 1.11 (s, 3H), 1.88 (dd, 1H, J= 7. 8,13. 2 Hz), 2.21 (dd, 1H, J=9. 2,13. 2 Hz), 3.12 (dd, 2H, J = 11. 5,23. 5 Hz), 4.22 (dd, 1H, J = 8.1, 8.9 Hz).

References:

WO2003/93279,2003,A1 Location in patent:Page/Page column 111