Methanol → 4-Hydroxy-L-proline methyl ester hydrochloride

Participants

Reaction Conditions

Reaction Steps

Acetyl chloride (249 mL, 3.47 mol) was added dropwise to methanol (2090 mL) with stirring and cooling to maintain the temperature below 30° C. After complete addition, stirring was continued for a further 60 min. before addition of trans-4-hydroxy-L-proline (325 g, 2.48 mol) as a solid. The reaction mixture was heated to reflux for 24 h, cooled to 0° C., and tert-butyl methyl ether (TBME, 5220 mL) was added slowly over 30 min. The precipitated solid was collected on a filter and washed with ice-cold TMBE (2×1 L). The product was dried at 40° C. overnight in a vacuum to yield 424 g of the desired ester.

Provenance & Evidence