Potassium Carbonate → 2-[4-(4-Pyrrolidin-1-yl-cyclohexyl)-phenyl]-8-oxa-2-aza-spiro[4.5]decan-1-one

HRID 1027423Notes

Reaction equation

HRID 1027423 reaction equation
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][O:9][CH2:8][CH2:7]2)[CH2:5][CH2:4][N:3]1[C:12]1[CH:17]=[CH:16][C:15]([C@@H:18]2[CH2:23][CH2:22][C@H:21](OS(C)(=O)=O)[CH2:20][CH2:19]2)=[CH:14][CH:13]=1.[NH:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[N:29]1([CH:21]2[CH2:22][CH2:23][CH:18]([C:15]3[CH:16]=[CH:17][C:12]([N:3]4[CH2:4][CH2:5][C:6]5([CH2:7][CH2:8][O:9][CH2:10][CH2:11]5)[C:2]4=[O:1])=[CH:13][CH:14]=3)[CH2:19][CH2:20]2)[CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 178505315HCID 178505315, compound2×

Product 1

HCID 545917692-[4-(4-Pyrrolidin-1-yl-cyclohexyl)-phenyl]-8-oxa-2-aza-spiro[4.5]decan-1-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Cis-Methanesulfonic acid 4-[4-(1-oxo-8-oxa-2-aza-spiro[4.5]dec-2-yl)-phenyl]-cyclohexyl ester (Intermediate 21) (30 mg, 0.07 mmol, 1 equiv.) and pyrrolidine (20 mg, 0.28 mmol, 4 equiv.) were dissolved in anhydrous CH3CN (2 mL). To this colorless solution was added powder K2CO3 at r.t. The suspension was heated in an oil bath maintained at 80° C. for 24 h. The suspension was concentrated to dryness. The residue was taken in water (2 mL) and DCM (2 mL). The two layers were separated, and the aqueous layer was extracted with DCM (2 mL×2). The combined DCM extracts were washed with sodium bicarbonate (2 mL), brine (2 mL), dried (anhydrous potassium carbonate), filtered, and concentrated in vacuo. The crude product was purified on a silica gel column, eluted with 5% of MeOH in DCM and 5% 7N NH3 of MeOH solution in DCM to obtain the title compound.

Workup

  1. temperatureThe suspension was heated in an oil bath
  2. concentrationThe suspension was concentrated to dryness
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with DCM (2 mL×2)
  5. washThe combined DCM extracts were washed with sodium bicarbonate (2 mL), brine (2 mL)
  6. dry with materialdried (anhydrous potassium carbonate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified on a silica gel column
  10. washeluted with 5% of MeOH in DCM and 5% 7N NH3 of MeOH solution in DCM

Sources & evidence

ORD record
ord-a8fec0b7c96542c891ff5f35791f568a
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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