tert-Butyl methyl ether → 2,3,4,6-Tetra-O-benzyl-1-O-carboxymethyl-mannopyranose

HRID 1265300Notes

Reaction equation

HRID 1265300 reaction equation
[CH2:1]([O:8][C@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:12][CH:10]1[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:45][C:46](=[O:49])[CH2:47]Cl)(C)(C)C.COC(C)(C)C>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.[OH-].[K+]>[CH2:1]([O:8][C@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C@@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[O:12][CH:10]1[O:11][CH2:47][C:46]([OH:49])=[O:45])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 15413tert-Butyl methyl etherHCID 66052tert-Butyl chloroacetateHCID 110169932,3,4,6-Tetra-O-benzyl-D-mannopyranose

Product 1

HCID 103041242,3,4,6-Tetra-O-benzyl-1-O-carboxymethyl-mannopyranose

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 1140TolueneSolventHCID 14797Potassium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture that consists of 54.1 g (100 mmol) of 2,3,4,6-tetra-O-benzyl-mannopyranose, 1.39 g (5 mmol) of tetrabutylammonium chloride in 350 ml of toluene and 150 ml of 50% aqueous potassium hydroxide solution is cooled to 0° C. At 0° C., 30.12 g (200 mmol) of chloroacetic acid-tert-butyl ester is added in drops over 20 minutes while being stirred vigorously. It is stirred for one hour at 10° C. 250 ml of methyl-tert-butyl ether is added, the organic phase is separated, and the aqueous phase is extracted twice with 250 ml of water. The solvent of the combined organic phases is distilled off in a vacuum, and the residue is taken up in 500 ml of ethanol. 40 ml of 50% aqueous sodium hydroxide solution is added, and it is refluxed for 0.5 hour. It is cooled to 0° C., set at pH 8 with 10% aqueous hydrochloric acid, and then the solvent is distilled off (vacuum). The residue is taken up in 300 ml of water and 500 ml of ethyl acetate, and the pH of the aqueous phase is set at 2 while being stirred (10% aqueous hydrochloric acid). The organic phase is separated, and the aqueous phase is extracted once more with 200 ml of ethyl acetate. The combined organic phases are dried on magnesium sulfate, the solvent is distilled off in a vacuum, and the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n=hexane/ethanol/acetic acid=20:5:3:0.5). The product-containing fractions are concentrated by evaporation, dissolved in 400 ml of ethyl acetate and shaken out three times with 200 ml of water. Then, the organic phase is separated and evaporated to the dry state in a vacuum.

Workup

  1. stirringIt is stirred for one hour at 10° C
  2. customthe organic phase is separated
  3. extractionthe aqueous phase is extracted twice with 250 ml of water
  4. distillationThe solvent of the combined organic phases is distilled off in a vacuum
  5. addition40 ml of 50% aqueous sodium hydroxide solution is added
  6. temperatureit is refluxed for 0.5 hour
  7. temperatureIt is cooled to 0° C.
  8. distillationthe solvent is distilled off (vacuum)
  9. stirringwhile being stirred (10% aqueous hydrochloric acid)
  10. customThe organic phase is separated
  11. extractionthe aqueous phase is extracted once more with 200 ml of ethyl acetate
  12. customThe combined organic phases are dried on magnesium sulfate
  13. distillationthe solvent is distilled off in a vacuum
  14. customthe residue is chromatographed on silica gel (mobile solvent: dichloromethane/n=hexane/ethanol/acetic acid=20:5:3:0.5)
  15. concentrationThe product-containing fractions are concentrated by evaporation
  16. dissolutiondissolved in 400 ml of ethyl acetate
  17. stirringshaken out three times with 200 ml of water
  18. customThen, the organic phase is separated
  19. customevaporated to the dry state in a vacuum

Sources & evidence

ORD record
ord-adf5df61e49c4276b6314b3908eb0711
Source dataset
uspto-grants-2003_04
Patent number
US06545135B2

Reaction notes

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