1,4-Dioxa-8-azaspiro(4.5)decane → 8-(2-Methoxypyridin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane

HRID 451533Notes

Reaction equation

HRID 451533 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.Cl[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([O:33][CH3:34])[CH:28]=1.[O:35]1[C:39]2([CH2:44][CH2:43][NH:42][CH2:41][CH2:40]2)[O:38][CH2:37][CH2:36]1.CC(C)([O-])C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:34][O:33][C:29]1[CH:28]=[C:27]([N:42]2[CH2:43][CH2:44][C:39]3([O:38][CH2:37][CH2:36][O:35]3)[CH2:40][CH2:41]2)[CH:32]=[CH:31][N:30]=1

Participants

7

Reactant 4

HCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 226385104-Chloro-2-methoxypyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 673434058-(2-Methoxypyridin-4-yl)-1,4-dioxa-8-azaspiro[4.5]decane

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
130 °C

Procedure

A solution of palladium(II) acetate (62.5 mg, 279 μmol) and 2-(dicyclohexylphosphino) biphenyl (201 mg, 557 μmol) in dioxane (1.5 mL) was stirred under argon at room temperature for 10 minutes, then added to a solution of 4-chloro-2-methoxypyridine (500 mg, 3.48 mmol), 1,4-dioxa-8-azaspiro[4.5]decane (499 mg, 446 μL, 3.48 mmol) and sodium tert-butoxide (502 mg, 5.22 mmol) in dioxane (1.5 mL), degassed and argon bubbled through the reaction during 5 minutes. The reaction mixture was heated in the microwave to 130° C. for 30 minutes. The reaction mixture was filtered through dicalite, water was added to the filtrate and the aqueous phase was extracted three times with ethyl acetate. The combined organic layers were dried over Na2SO4 and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, 70 g, 80% to 100% ethyl acetate in heptane). The title compound was obtained as brown oil (700 mg, 80%).

Workup

  1. customdegassed
  2. customargon bubbled through the reaction during 5 minutes
  3. filtrationThe reaction mixture was filtered through dicalite, water
  4. additionwas added to the filtrate
  5. extractionthe aqueous phase was extracted three times with ethyl acetate
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. customthe solvent was evaporated
  8. customThe residue was purified by flash chromatography (silica gel, 70 g, 80% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-f98662627a0b4c1eba8b41e459c6e905
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

Loading…