Methanol → Methyl 4-[(3S,5aR,6S,7R,8aS)-6-ethynyl-7-(tetrahydro-2H-pyran-2-yloxy)octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoate

HRID 573535Notes

Reaction equation

HRID 573535 reaction equation
CO.[CH:3]([C@@H:5]1[C@@H:14]2[C@@H:8]([O:9][CH2:10][C@@H:11]([CH2:15][CH2:16][CH2:17][C:18]([O:20][CH:21](C)C)=[O:19])[CH2:12][CH2:13]2)[CH2:7][C@H:6]1[O:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][O:26]1)=O.[C:31](=O)([O-])[O-].[K+].[K+].C/C(/[O-])=C(/P(OC)(OC)=O)\[N+]#N>C(OCC)(=O)C>[C:3]([C@@H:5]1[C@@H:14]2[C@@H:8]([O:9][CH2:10][C@@H:11]([CH2:15][CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])[CH2:12][CH2:13]2)[CH2:7][C@H:6]1[O:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][O:26]1)#[CH:31]

Participants

6

Reactant 4

HCID 887MethanolHCID 11430Potassium Carbonate2×HCID 866653202-Propanyl 4-[(3S,5aR,6R,7R,8aS)-6-formyl-7-(tetrahydro-2H-pyran-2-yloxy)octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoateHCID 178502985HCID 178502985, compound2×

Product 1

HCID 86704363Methyl 4-[(3S,5aR,6S,7R,8aS)-6-ethynyl-7-(tetrahydro-2H-pyran-2-yloxy)octahydro-2H-cyclopenta[b]oxepin-3-yl]butanoateYield 28.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a methanol solution (2.3 mL) of the compound (180 mg) produced in Example 13, potassium carbonate (94 mg) and a Bestmann reagent (dimethyl-1-diazo-2-oxopropyl phosphonate) (105 mg) were added, followed by stirring at room temperature for 6 hours. Further, potassium carbonate (47 mg) and the Bestmann reagent (53 mg) were added, followed by stirring at room temperature overnight. The reaction mixture was cooled to 0° C.; diluted with ethyl acetate; and then separated by adding water. The organic layer was washed with water and a saturated saline; dried with magnesium sulfate; then filtered; and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=97:3→65:35) to obtain a titled compound (47 mg) having the following physical property values.

Workup

  1. stirringby stirring at room temperature overnight
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. customand then separated
  4. additionby adding water
  5. washThe organic layer was washed with water
  6. dry with materialdried with magnesium sulfate
  7. filtrationthen filtered
  8. concentrationand concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=97:3→65:35)

Sources & evidence

ORD record
ord-441e73aeea2a42b6aedb923002fc8850
Source dataset
uspto-grants-2015_05
Patent number
US09029574B2

Reaction notes

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