ethyl [(2R*,6S*)-2-(4-fluorophenyl)-6-vinylpiperidin-1-yl]oxoacetate → (6R*,9aS*)-6-(4-fluorophenyl)-3-hydroxyhexahydropyrido[2,1-c][1,4]oxazin-4-one

HRID 1436091Notes

Reaction equation

HRID 1436091 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H:10](C=C)[N:9]2[C:16](=[O:22])[C:17]([O:19][CH2:20]C)=[O:18])=[CH:4][CH:3]=1>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[N:9]3[C@H:10]([CH2:20][O:19][CH:17]([OH:18])[C:16]3=[O:22])[CH2:11][CH2:12][CH2:13]2)=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 86612603ethyl [(2R*,6S*)-2-(4-fluorophenyl)-6-vinylpiperidin-1-yl]oxoacetate

Product 1

HCID 69010340(6R*,9aS*)-6-(4-fluorophenyl)-3-hydroxyhexahydropyrido[2,1-c][1,4]oxazin-4-oneYield 13.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of ethyl [(2R*,6S*)-2-(4-fluorophenyl)-6-vinylpiperidin-1-yl]oxoacetate (220 mg) in methanol (5 mL) was cooled to −78° C., and ozone gas was bubbled through the reaction solution for 20 minutes. Sodium borohydride (164 mg) was added to the reaction solution while stirring at −78° C., and the reaction solution was stirred at that temperature for 30 minutes. Ethyl acetate and a saturated ammonium chloride solution were added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 26 mg of the title compound. The property values of the compound are as follows.

Workup

  1. customozone gas was bubbled through the reaction solution for 20 minutes
  2. additionSodium borohydride (164 mg) was added to the reaction solution
  3. stirringthe reaction solution was stirred at that temperature for 30 minutes
  4. additionEthyl acetate and a saturated ammonium chloride solution were added to the reaction solution
  5. customthe organic layer was separated
  6. dry with materialThe resulting organic layer was dried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (elution solvent: heptane:ethyl acetate=1:1->ethyl acetate)

Sources & evidence

ORD record
ord-cf8f8280c320409aae249328fcbf6b4a
Source dataset
uspto-grants-2009_11
Patent number
US07618960B2

Reaction notes

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