1,4-Dioxane → 8-[4-(Benzyloxy)phenyl]-1,4-dioxa-8-azaspiro[4,5]decane

HRID 1095831Notes

Reaction equation

HRID 1095831 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22](I)=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CC(C)([O-])C.[Na+].O1CCOCC1>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1>[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([N:8]2[CH2:9][CH2:10][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:6][CH2:7]2)=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 5196711-(Benzyloxy)-4-iodobenzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 667839188-[4-(Benzyloxy)phenyl]-1,4-dioxa-8-azaspiro[4,5]decaneYield 73.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 8857Ethyl AcetateSolvent

Procedure

1,4-Dioxa-8-azaspiro[4,5]decane (653 g, 4.56 mol), 1-(benzyloxy)-4-iodobenzene (1 kg, 3.8 mol), sodium tert-butoxide (511 g, 5.32 mol), Pd(OAc)2 (17 g, 76 mmol) and biphenyl-2-yl(dicyclohexyl) phosphine (54 g, 152 mmol) were mixed, and 1,4-dioxane, this was stirred overnight at 80° C. in a nitrogen atmosphere. The reaction solution was cooled with ice, diluted with ethyl acetate, washed with water and saturated saline in that order, and the organic layer was dried with sodium sulfate. The solvent was evaporated off under reduced pressure, and the resulting residue was purified through silica gel column chromatography (eluate: chloroform/ethyl acetate=10/1), and the resulting crude product was suspended in a mixed solvent of chloroform/hexane and filtered under suction to obtain the entitled compound (910 g, 73%) as a brown solid.

Workup

  1. temperatureThe reaction solution was cooled with ice
  2. washwashed with water and saturated saline in that order
  3. dry with materialthe organic layer was dried with sodium sulfate
  4. customThe solvent was evaporated off under reduced pressure
  5. customthe resulting residue was purified through silica gel column chromatography (eluate: chloroform/ethyl acetate=10/1)
  6. filtrationfiltered under suction

Sources & evidence

ORD record
ord-3f38e67ac883422d94ff3de7db0e18b0
Source dataset
uspto-grants-2012_03
Patent number
US08138206B2

Reaction notes

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