Water → 4-(Hydroxymethyl)oxane-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of lithium hydroxide monohydrate (4.46 Kg) in methanol (44 liters) and water (11 Kg) was added ethyl 4-hydroxymethyl-tetrahydropyran-4-carboxylate (8.0 Kg) The mixture was refluxed for 30 minutes, then solvent removed under reduced pressure. The mixture was cooled to 20° C., methyl tert-butyl ether (14.8 Kg) added, stirred for 10 minutes, and allowed to settle. The top organic layer was separated. This was repeated twice more, then the remaining mixture cooled to -10° C., and a solution of 31% hydrochloric acid (13 Kg) in water (3 Kg) added, maintaining the temperature below 5° C. The mixture was extracted several times with tetrahydrofuran, and the combined organic phases dried over magnesium sulfate. Approximately 90% of the tetrahydrofuran was removed, and the remaining solution added to a mixture of hexane (64.5 Kg) and methyl tert-butylether (23.7 Kg) with stirring. The precipitated solid material was filtered off and dried under reduced pressure at 60° C., to give 4-hydroxymethyl-tetrahydropyran-4-carboxylic acid (3.7 Kg), the compound of Formula (9a).

Provenance & Evidence