1,4-Dioxa-8-azaspiro(4.5)decane → 8-(4-Chloro-3-methoxyphenyl)-1,4-dioxa-8-azaspiro[4.5]decane

HRID 1804851Notes

Reaction equation

HRID 1804851 reaction equation
CC(C)([O-])C.[Na+].[O:7]1[C:11]2([CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[O:10][CH2:9][CH2:8]1.Br[C:18]1[CH:19]=[CH:20][C:21]([Cl:26])=[C:22]([O:24][CH3:25])[CH:23]=1>CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd].C1(C)C=CC=CC=1.CC(O)(C)C>[Cl:26][C:21]1[CH:20]=[CH:19][C:18]([N:14]2[CH2:15][CH2:16][C:11]3([O:10][CH2:9][CH2:8][O:7]3)[CH2:12][CH2:13]2)=[CH:23][C:22]=1[O:24][CH3:25]

Participants

6

Reactant 3

HCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 27695675-Bromo-2-chloroanisoleHCID 23676156Sodium t-butoxide

Product 1

HCID 685538928-(4-Chloro-3-methoxyphenyl)-1,4-dioxa-8-azaspiro[4.5]decaneYield 70%

Reagents, catalysts & solvents 2

HCID 119822622-(2'-Di-tert-butylphosphine)biphenylpalladium(II) acetateCatalystHCID 22595558Toluene tert-butyl alcoholSolvent

Conditions

Temperature
160 °C

Procedure

A 20-mL microwave vial was charged with sodium tert-butoxide (537 mg, 5.59 mmol), acetato(2′-di-t-butylphosphino-1,1′-biphenyl-2-yl)palladium (II) (259 mg, 0.559 mmol) and a stir bar. The vial was sealed and purged with nitrogen. A solution of 1,4-dioxa-8-azaspiro[4.5]decane (800 mg, 5.59 mmol) and 5-bromo-2-chloroanisole (1361 mg, 6.15 mmol) in 5:1 toluene/t-BuOH (12 mL) was added via syringe. The mixture was heated by microwave (300 W) at 160° C. for 10 min and then cooled and partitioned between EtOAc and brine. The aqueous phase was extracted with EtOAc and the organic phases were combined. The resultant solution was dried (Na2SO4) and concentrated on a rotary evaporator to give the crude product. The crude product was purified by flash chromatography using a 40 g silica gel cartridge column and gradient elution with EtOAc/hexanes to afford 8-(4-chloro-3-methoxyphenyl)-1,4-dioxa-8-azaspiro[4.5]decane (1.1 g, 70%) as a yellow solid.

Workup

  1. customThe vial was sealed
  2. custompurged with nitrogen
  3. temperaturecooled
  4. custompartitioned between EtOAc and brine
  5. extractionThe aqueous phase was extracted with EtOAc
  6. dry with materialThe resultant solution was dried (Na2SO4)
  7. concentrationconcentrated on a rotary evaporator
  8. customto give the crude product
  9. customThe crude product was purified by flash chromatography
  10. washa 40 g silica gel cartridge column and gradient elution with EtOAc/hexanes

Sources & evidence

ORD record
ord-5d1b795c616f459f9c06192e76b379db
Source dataset
uspto-grants-2013_01
Patent number
US08354432B2

Reaction notes

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