Acetoacetic Acid → HCID 22870402, compound

HRID 1885710Notes

Reaction equation

HRID 1885710 reaction equation
[C:1]1([CH2:7][O:8][CH2:9][C@@H:10]2[C@@H:15]([CH2:16][O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:14][CH:12](O)[C@@H:11]2[OH:25])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(CC(O)=O)=O.C[Si](Br)(C)C.[H-].C([Al+]CC(C)C)C(C)C>ClCCl.C1(C)C=CC=CC=1>[C:1]1([CH2:7][O:8][CH2:9][C@@H:10]2[C@@H:15]([CH2:16][O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:14][CH2:12][C@@H:11]2[OH:25])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 96Acetoacetic Acid2×HCID 76113BromotrimethylsilaneHCID 10450186HCID 10450186, compound2×HCID 21225700Diisobutylaluminumhydride

Product 1

HCID 22870402HCID 22870402, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-deoxy-3-[(phenylmethoxy)methyl]-5-O-(phenylmethyl)-D-ribofuranose, diacetate (4.81 g, 11.23 mmol) in dichloromethane (100 ml) at 0° C. was added trimethylsilyl bromide (2.59 ml, 19.65 mmol). The reaction was stirred at 0° C. for 30 minutes and at room temperature for 6.5 hours. At this time, the reaction was cooled to 0° C. and transferred via canula to a toluene solution of diisobutylaluminum hydride (100 ml, 1M), also at 0° C. The reaction mixture was kept at 0° C. for 40 minutes and then quenched cautiously with methanol (14.2 ml) and then water (20 ml). After stirring at room temperature for 1 hour, the mixture was filtered through Celite, washing well with ether and ethyl acetate. The volatiles were evaporated in vacuo and the resulting oil (4.04 g) was combined with the crude product (7.6 g) from an identical reaction starting with 23.16 mmol of 3-deoxy-3[(phenylmethoxy)methyl]-5-O-(phenylmethyl)-D-ribofuranose, diacetate. The combined products were purified by flash chromatography (Merck silica gel-60, 230-400 mesh) eluting with a step-wise gradient of dichloromethane and dichloromethane/dioxane (20:1 and then 7:3). The resulting material was further purified by flash chromatography (Merck silica gel-60, 230-400 mesh) eluting with dichloromethane/dioxane (15:1) to give the title compound as a colorless oil (3.4 g). The mixed fractions were purified by flash chromatography (Merck silica gel-60, 230-400 mesh) eluting with dichloromethane/dioxane (20:1) to give additional title compound as a colorless oil (1.5 g pure and 1.66 g ~90% pure by 1H NMR).

Workup

  1. temperatureAt this time, the reaction was cooled to 0° C.
  2. waitThe reaction mixture was kept at 0° C. for 40 minutes
  3. customquenched cautiously with methanol (14.2 ml)
  4. stirringAfter stirring at room temperature for 1 hour
  5. filtrationthe mixture was filtered through Celite
  6. washwashing well with ether and ethyl acetate
  7. customThe volatiles were evaporated in vacuo
  8. customthe resulting oil (4.04 g) was combined with the crude product (7.6 g) from an identical reaction
  9. customThe combined products were purified by flash chromatography (Merck silica gel-60, 230-400 mesh)
  10. washeluting with a step-wise gradient of dichloromethane and dichloromethane/dioxane (20:1
  11. customThe resulting material was further purified by flash chromatography (Merck silica gel-60, 230-400 mesh)
  12. washeluting with dichloromethane/dioxane (15:1)

Sources & evidence

ORD record
ord-c9097a6bdf4045b7a4ab39d731685cef
Source dataset
uspto-grants-1992_09
Patent number
US05145960

Reaction notes

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