Ethanol → 2,3,4,6-Tetra-O-benzyl-1-O-carboxymethyl-mannopyranose

HRID 1072286Notes

Reaction equation

HRID 1072286 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.[OH-].[K+].C([O:47][C:48](=[O:51])[CH2:49]Br)(C)(C)C.C(O)C>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(OCOCC)C.O>[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][CH2:49][C:48]([OH:51])=[O:47])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 702EthanolHCID 14797Potassium Hydroxide2×HCID 79177tert-Butyl bromoacetateHCID 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 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 10024DiethoxymethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture that consists of 500.0 g (924.2 mmol) of 2,3,4,6-tetra-O-benzyl-mannopyranose and 50.00 g (147.1 mmol) of tetrabutylammonium hydrogen sulfate in 2500 ml of diethoxymethane is cooled to a temperature of 0° C. 121.77 g (217.0 mmol) of fine-powder potassium hydroxide is then added thereto, and it is stirred for 10 more minutes. At a temperature of between 0° C. and 5° C., 180.39 g (1608 mmol) of bromoacetic acid tert-butyl ester is added in drops within 30 minutes while being stirred vigorously. Stirring is continued for two hours at 0° C. It is then allowed to reach room temperature within two hours, 500 ml of absolute ethanol (denaturized with cyclohexane) is added thereto, and the solvent is largely distilled off at a bath temperature of 105° C. 1000 ml of ethanol (absolute, denaturized with cyclohexane) is now added thereto, and the solvent is largely distilled off again at a bath temperature of 105° C. 1000 ml of ethanol (absolute, denaturized with cyclohexane) is again added thereto, as well as 60.89 g (1085 mmol) of potassium hydroxide (as a powder) as well as 1000 ml of completely demineralized water. It is refluxed for 7 hours and then concentrated by evaporation to an oil that can still be stirred. After cooling to room temperature, the residue is extracted 3 times with 500 ml each of hexane. The aqueous phase is mixed with 500 ml of MTB and set at a pH of 2 while being stirred vigorously with 37% hydrochloric acid. The aqueous phase is then extracted twice with 1000 ml each of MTB. The organic phases are combined, dried and evaporated to the dry state in a rotary evaporator at a bath temperature of 50° C. and a pressure of 70 mbar. The residue is chromatographed on 1000 g of silica gel 60 (grain size 40-63 μm). As an eluant, 2700 ml of nhexane, 5400 ml of dichloromethane as well as 1500 ml of methanol are used. The product-containing fractions are combined and evaporated to the dry state in a vacuum.

Workup

  1. stirringwhile being stirred vigorously
  2. stirringStirring
  3. waitto reach room temperature within two hours
  4. distillationthe solvent is largely distilled off at a bath temperature of 105° C
  5. addition1000 ml of ethanol (absolute, denaturized with cyclohexane) is now added
  6. distillationthe solvent is largely distilled off again at a bath temperature of 105° C
  7. addition1000 ml of ethanol (absolute, denaturized with cyclohexane) is again added
  8. temperatureIt is refluxed for 7 hours
  9. concentrationconcentrated by evaporation to an oil that
  10. stirringcan still be stirred
  11. temperatureAfter cooling to room temperature
  12. extractionthe residue is extracted 3 times with 500 ml each of hexane
  13. additionThe aqueous phase is mixed with 500 ml of MTB
  14. stirringwhile being stirred vigorously with 37% hydrochloric acid
  15. extractionThe aqueous phase is then extracted twice with 1000 ml each of MTB
  16. customdried
  17. customevaporated to the dry state in a rotary evaporator at a bath temperature of 50° C.
  18. customThe residue is chromatographed on 1000 g of silica gel 60 (grain size 40-63 μm)
  19. customevaporated to the dry state in a vacuum

Sources & evidence

ORD record
ord-768973e27ca24ce4b50af0e7688d5379
Source dataset
uspto-grants-2005_06
Patent number
US06908989B2

Reaction notes

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