tert-Butanol → Methyl-3-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)benzoate

HRID 338671Notes

Reaction equation

HRID 338671 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].CC(O)(C)C.[CH2:12]1[O:21][C:15]2([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[O:14][CH2:13]1.[CH3:22][O:23][C:24](=[O:32])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27](Br)[CH:26]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH3:22][O:23][C:24](=[O:32])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([N:18]2[CH2:19][CH2:20][C:15]3([O:21][CH2:12][CH2:13][O:14]3)[CH2:16][CH2:17]2)[CH:26]=1

Participants

8

Reactant 4

HCID 6386tert-Butanol2×HCID 10796Cesium carbonateHCID 12070Methyl 3-bromobenzoateHCID 674351,4-Dioxa-8-azaspiro(4.5)decane

Product 1

HCID 60059302Methyl-3-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)benzoateYield 97.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
120 °C

Procedure

Procedure adopted from Tetrahedron Lett., 2007, 48, 2519. A thick-walled glass reaction vessel was charged with palladium(II)acetate (235 mg, 1.05 mmol), X-Phos (500 mg, 1.05 mmol, 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl), cesium carbonate (6.82 g, 20.95 mmol) and 5:1 (v/v) toluene:t-BuOH (20 mL). The stirred contents were purged with nitrogen and a solution of 4-piperidone ethylene ketal (2.70 mL, 20.95 mmol) and methyl-3-bromobenzoate (4.95 g, 23.02 mmol) in 5:1 (v/v) toluene:t-BuOH (100 mL) was added. After stirring for 2 minutes, the vessel was sealed and the reaction mixture was heated at 120° C. for 16 hours. Upon cooling to room temperature, the reaction mixture was filtered through celite and the filtrate was concentrated. Elution through a flash column (silica gel 60, 230-400 mesh, 7:3 hexanes:EtOAc) followed by concentration gave the title compound as an oil (5.64 g, 97%).

Workup

  1. customA thick-walled glass reaction vessel
  2. customThe stirred contents were purged with nitrogen
  3. customthe vessel was sealed
  4. temperatureUpon cooling to room temperature
  5. filtrationthe reaction mixture was filtered through celite
  6. concentrationthe filtrate was concentrated
  7. washElution through a flash column (silica gel 60, 230-400 mesh, 7:3 hexanes:EtOAc)
  8. concentrationfollowed by concentration

Sources & evidence

ORD record
ord-761c5256799d4ab7bd44e14652109788
Source dataset
uspto-grants-2014_11
Patent number
US08889870B2

Reaction notes

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