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

HRID 1584418Notes

Reaction equation

HRID 1584418 reaction equation
O.[OH-].[Li+].O.[OH:5][CH2:6][C:7]1([C:13]([O:15]CC)=[O:14])[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1>CO>[OH:5][CH2:6][C:7]1([C:13]([OH:15])=[O:14])[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 22439651Ethyl 4-(hydroxymethyl)oxane-4-carboxylate

Product 1

HCID 179000864-(Hydroxymethyl)oxane-4-carboxylic acidYield 54.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

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).

Workup

  1. temperaturewas refluxed for 30 minutes
  2. customsolvent removed under reduced pressure
  3. additionmethyl tert-butyl ether (14.8 Kg) added
  4. customThe top organic layer was separated
  5. temperaturethe remaining mixture cooled to -10° C.
  6. additiona solution of 31% hydrochloric acid (13 Kg) in water (3 Kg) added
  7. temperaturemaintaining the temperature below 5° C
  8. extractionThe mixture was extracted several times with tetrahydrofuran
  9. dry with materialthe combined organic phases dried over magnesium sulfate
  10. customApproximately 90% of the tetrahydrofuran was removed
  11. additionthe remaining solution added to a mixture of hexane (64.5 Kg) and methyl tert-butylether (23.7 Kg)
  12. stirringwith stirring
  13. filtrationThe precipitated solid material was filtered off
  14. customdried under reduced pressure at 60° C.

Sources & evidence

ORD record
ord-979051ca39de4105aee9f6bf68823cb0
Source dataset
uspto-grants-1999_08
Patent number
US05932595

Reaction notes

Loading…