Tert-butyl 3-bromo-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)benzoate → Tert-butyl 3-(5-methylpyridin-2-yl)-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)benzoate

HRID 1257553Notes

Reaction equation

HRID 1257553 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]2[CH2:22][C:18]3([CH2:21][CH2:20][CH2:19]3)[O:17][N:16]=2)[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Br-].[CH3:24][C:25]1[CH:26]=[CH:27][C:28]([Zn+])=[N:29][CH:30]=1>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:24][C:25]1[CH:26]=[CH:27][C:28]([C:2]2[CH:3]=[C:4]([CH:12]=[C:13]([C:15]3[CH2:22][C:18]4([CH2:21][CH2:20][CH2:19]4)[O:17][N:16]=3)[CH:14]=2)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])=[N:29][CH:30]=1

Participants

5

Reactant 2

HCID 58096138Tert-butyl 3-bromo-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)benzoateHCID 178427808HCID 178427808, compound

Product 1

HCID 66896093Tert-butyl 3-(5-methylpyridin-2-yl)-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)benzoateYield 96.7%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl 3-bromo-5-(5-oxa-6-azaspiro[3.4]oct-6-en-7-yl)benzoate (1.42 g, 3.88 mmol) and bis(tri-tert-butylphosphine)palladium(0) (59.0 mg, 0.12 mmol) in dioxane (20 mL) was added 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 15.5 mL, 7.75 mmol). The reaction mixture was heated to 70° C. After 1 h, the reaction was cooled to ambient temperature and the solvent was evaporated. Saturated aqueous sodium potassium tartrate was adde and the mixture was extracted with ethyl acetae (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→75% hexanes/ethyl acetate) gave the title compound (1.42 g). MS 379.2 (M+1).

Workup

  1. temperaturethe reaction was cooled to ambient temperature
  2. customthe solvent was evaporated
  3. additionSaturated aqueous sodium potassium tartrate was adde
  4. extractionthe mixture was extracted with ethyl acetae (3×)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (100% hexanes→75% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-149b8c217ed04d2c820760522d005ed3
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

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