D-valine dane salt synthesis

Yield:-

Reaction Conditions:

with potassium hydroxide in isopropyl alcohol for 2 h;Heating / reflux;

Steps:

1.G G.
N-(3-Methoxy-1-methyl-3-oxo-1-propenyl)-R-valine, potassium salt (R-valine Dane salt) 36.6 g solid KOH are dissolved in 1250 ml of 2-propanol with slight warming. 65 g R-valine and 65.9 ml of methyl acetoacetate are added. The mixture is stirred and refluxed for 2 h. The reflux condenser is replaced by a Claisen condenser and a short column and the water formed during the condensation reaction is removed by distilling off about 1 I 2-propanol. Thereafter 500 ml of 2-propanol are added and again 500 ml are distilled off. The warm solution is poured into 3 I of MTBE and stirred with ice-cooling for about 3 h. The resulting suspension is left overnight at 4 °C (moisture excluded), filtered, washed with 500 ml of MTBE and dried to yield N-(3-methoxy-1-methyl-3-oxo-1-propenyl)-R-valine potassium salt.

References:

Nabriva Therapeutics Forschungs GmbH EP1908750, 2008, A1 Location in patent:Page/Page column 7