Sodium Carbonate → 2-(1,4-Dioxa-spiro[4.5]dec-7-en-8-yl)-pyridin-3-ol

HRID 2175483Notes

Reaction equation

HRID 2175483 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:18][CH2:17][C:12]3([O:16][CH2:15][CH2:14][O:13]3)[CH2:11][CH:10]=2)O1.I[C:21]1[C:26]([OH:27])=[CH:25][CH:24]=[CH:23][N:22]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1(P([Pd-4](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:13]1[C:12]2([CH2:17][CH2:18][C:9]([C:21]3[C:26]([OH:27])=[CH:25][CH:24]=[CH:23][N:22]=3)=[CH:10][CH2:11]2)[O:16][CH2:15][CH2:14]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 971792-Iodopyridin-3-olHCID 36970768-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dioxaspiro(4.5)dec-7-ene

Product 1

HCID 585625152-(1,4-Dioxa-spiro[4.5]dec-7-en-8-yl)-pyridin-3-ol

Reagents, catalysts & solvents 2

HCID 178420553HCID 178420553, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

8-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,4-dioxa-spiro[4.5]dec-7-ene (prepared as described in PCT Int. Appl. WO2006064189, 0.292 g, 1.10 mmol), 2-iodo-3-hydroxypyridine (Aldrich, 0.177 g, 0.801 mmol), and tetrakis (triphenylphosphino)palladium(0) (Aldrich, 0.048 g, 0.042 mmol) were dissolved in 1,4-dioxane (9 mL), treated with 2M aqueous Na2CO3 (2.0 mL, 4.0 mmol), bubbled with argon for a few minutes, and heated to 100° C. under reflux condenser for 24 h. After cooling to ambient temperature, the reaction was diluted with water (30 mL), extracted thrice with dichloromethane, aqueous layer acidified to ca. pH 7, extracted twice more with dichloromethane, and the combined organic layers washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give an orange oil. This was purified by thin layer chromatography on silica gel (EtOAc) to give the title compound as a yellow solid.

Workup

  1. custombubbled with argon for a few minutes
  2. temperatureunder reflux condenser for 24 h
  3. temperatureAfter cooling to ambient temperature
  4. additionthe reaction was diluted with water (30 mL)
  5. extractionextracted thrice with dichloromethane, aqueous layer
  6. extractionextracted twice more with dichloromethane
  7. washthe combined organic layers washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give an orange oil
  12. customThis was purified by thin layer chromatography on silica gel (EtOAc)

Sources & evidence

ORD record
ord-760219d7363a442abbed451adeb17ce0
Source dataset
uspto-grants-2015_06
Patent number
US09062048B2

Reaction notes

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