(3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate → HCID 57857028, compound

HRID 561737Notes

Reaction equation

HRID 561737 reaction equation
[C:1]([O:9][C@@H:10]1[CH2:18][C@@H:13]2[O:14][C:15](=[O:17])[CH2:16][C@@H:12]2[C@H:11]1[CH:19]=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:21]1[C:25]([C:26](=[O:36])[CH2:27]P(=O)(OCC)OCC)=[CH:24][C:23]2[CH:37]=[CH:38][CH:39]=[CH:40][C:22]1=2>C(Cl)Cl.[Cl-].[Li+].C1COCC1>[C:1]([O:9][C@@H:10]1[CH2:18][C@@H:13]2[O:14][C:15](=[O:17])[CH2:16][C@@H:12]2[C@H:11]1/[CH:19]=[CH:27]/[C:26]([C:25]1[S:21][C:22]2[CH:40]=[CH:39][CH:38]=[CH:37][C:23]=2[CH:24]=1)=[O:36])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 11000244(3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoateHCID 86633823HCID 86633823, compound

Product 1

HCID 57857028HCID 57857028, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 433294Lithium ChlorideSolvent

Conditions

Temperature
-20 °C

Procedure

A reactor equipped with a mechanical stirrer, under nitrogen, is charged with (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate (99.2 g, 0.362 mol) in DCM and lithium chloride (1 molar equivalent) dissolved in THF. Diethyl 2-(benzo[b]thiophen-2-yl)-2-oxoethylphosphonate (1 molar equivalent) is added neat and rinsed with DCM. Some lithium chloride precipitates from solution when the THF and DCM solutions are mixed. The mixture is stirred under nitrogen and cooled to −20° C. After adding the phosphonate and subsequent stirring and cooling, the lithium chloride dissolved. After stirring for 2.5 hours, triethylamine (1 molar equivalent) is added neat via addition funnel and the temperature is held at −5° C. and stirred at this temperature for 19 hours. The temperature is adjusted to 0° C. and treated with 5% aqueous citric acid and the layers are separated. The organic layer is dried over magnesium sulfate and filtered. The crude product is purified on silica gel, eluted with ethyl acetate-hexanes (1:1) to afford the title intermediate 4a.

Workup

  1. customA reactor equipped with a mechanical stirrer, under nitrogen
  2. washrinsed with DCM
  3. customSome lithium chloride precipitates from solution when the THF and DCM solutions
  4. additionare mixed
  5. additionAfter adding the phosphonate
  6. stirringsubsequent stirring
  7. temperaturecooling
  8. dissolutionthe lithium chloride dissolved
  9. stirringAfter stirring for 2.5 hours
  10. additiontriethylamine (1 molar equivalent) is added neat via addition funnel
  11. customis held at −5° C.
  12. stirringstirred at this temperature for 19 hours
  13. customis adjusted to 0° C.
  14. additiontreated with 5% aqueous citric acid
  15. customthe layers are separated
  16. dry with materialThe organic layer is dried over magnesium sulfate
  17. filtrationfiltered
  18. customThe crude product is purified on silica gel
  19. washeluted with ethyl acetate-hexanes (1:1)

Sources & evidence

ORD record
ord-f59dda016a314a9388012049eb966622
Source dataset
uspto-grants-2011_11
Patent number
US08063240B2

Reaction notes

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