Magnesium → Nitrogen

HRID 644923Notes

Reaction equation

HRID 644923 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[O:14][CH2:13][CH2:12][CH2:11][O:10]2)=[CH:5][CH:4]=1.O1CCCOC1C1C=CC([Mg]Br)=CC=1.Cl[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36]1[N:37]=[N:38][N:39]([CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][O:42]2)[N:40]=1.ClC1C=CC=CC=1C1N(C2CCCCO2)N=NN=1>O1CCCC1.BrCCBr.COCCOC.Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1.[Cl-].[Zn+2].[Cl-]>[N:37]#[N:38].[O:10]1[CH2:11][CH2:12][CH2:13][O:14][CH:9]1[C:6]1[CH:7]=[CH:8][C:3]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:36]2[N:37]=[N:38][N:39]([CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)[N:40]=2)=[CH:4][CH:5]=1

Participants

12

Reactant 5

HCID 5462224Magnesium2×HCID 110756432-(4-Bromophenyl)-1,3-dioxane2×HCID 675464055-(2-chlorophenyl)-1-(tetrahydropyran-2-yl)-1H-tetrazoleHCID 675468845-(2-Chlorophenyl)-2-(oxan-2-yl)-2H-tetrazoleHCID 178419619HCID 178419619, compound2×

Product 2

HCID 947NitrogenHCID 686267825-(4'-[1,3]dioxan-2-yl-biphenyl-2-yl)-2-(tetrahydro-pyran-2-yl)-2H-tetrazole

Reagents, catalysts & solvents 5

HCID 78391,2-DibromoethaneCatalystHCID 3007855ZincchlorideCatalystHCID 178418745HCID 178418745, compoundCatalystHCID 8028TetrahydrofuranSolvent3×HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
10 °C

Procedure

A suspension of magnesium turnings (2.68 g) in anhydrous tetrahydrofuran (20 mL) is cooled to 10° C. and five drops of 1,2-dibromoethane are added. 2 mL of a solution of 2-(4-bromo-phenyl)-[1,3]dioxane (24.3 g; 100 mmol) in anhydrous tetrahydrofuran (80 mL) is added at 10° C. under vigorous stirring. After the reaction starts the remainder of the solution of 2-(4-bromo-phenyl)-[1,3]dioxane is added over 90 minutes. The resulting mixture is further stirred at about 16° C. for 2 hours and at 25° C. for 75 minutes. The concentration of 4-([1,3]dioxan-2-yl)phenylmagnesium bromide in the solution above the excess of magnesium turnings is about 0.90 M. In another flask, dichloro[1,3-bis(diphenylphosphino)propane]nickel(II) (0.054 g; 0.10 mmol) is suspended in 1,2-dimethoxyethane (7.7 mL) and cooled to about 0° C. before a 0.5 M solution of zinc chloride in tetrahydrofuran (1.0 mL; 0.50 mmol) and a solution of a mixture of 5-(2-chlorophenyl)-2-(tetrahydropyran-2-yl)-2H-tetrazole and 5-(2-chlorophenyl)-1-(tetrahydropyran-2-yl)-1H-tetrazole (2.65 g; 10.0 mmol) in 1,2-dimethoxyethane (2.7 mL) are added. To the vigorously stirred resulting suspension is added at about 0° C. 13.4 mL of the above 0.90 M 4-([1,3]dioxan-2-yl)phenylmagnesium bromide solution (12.0 mmol) over one hour. The resulting brown-yellow solution is allowed to warm up and further stirred at room temperature for 3 hours. The mixture is cooled to about 0° C. and quenched with a 7.5% solution of ammonium chloride in water (20 mL). The aqueous phase is separated and extracted with ethyl acetate (50 mL). The combined organic phases are washed with water (20 mL), a 7.5 % solution of sodium carbonate in water (20 mL) and water (20 mL). The combined organic phases are evaporated in vacuo. A solution of the resulting oil in a small amount of ethyl acetate is filtered and evaporated. The resulting oil is purified by column chromatography on silica gel eluting with a 1:2 mixture of ethyl acetate and hexane to afford the main isomer (N2-isomer) 5-(4′-[1,3]dioxan-2-yl-biphenyl-2-yl2-(tetrahydro-pyran-2-yl)-2H-tetrazole as a colorless oil and the minor isomer (N1-isomer) 5-(4′-[1,3]dioxan-2-yl-biphenyl-2-yl)-1-(tetrahydro-pyran-2-yl)-1H-tetrazole as colorless crystals.

Workup

  1. additionis added over 90 minutes
  2. additionare added
  3. stirringTo the vigorously stirred
  4. customresulting suspension
  5. additionis added at about 0° C
  6. temperatureto warm up
  7. stirringfurther stirred at room temperature for 3 hours
  8. temperatureThe mixture is cooled to about 0° C.
  9. customquenched with a 7.5% solution of ammonium chloride in water (20 mL)
  10. customThe aqueous phase is separated
  11. extractionextracted with ethyl acetate (50 mL)
  12. washThe combined organic phases are washed with water (20 mL)
  13. customThe combined organic phases are evaporated in vacuo
  14. filtrationA solution of the resulting oil in a small amount of ethyl acetate is filtered
  15. customevaporated
  16. customThe resulting oil is purified by column chromatography on silica gel eluting with a 1:2 mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-109df11916f14493aea77537f68c2a26
Source dataset
uspto-grants-2010_04
Patent number
US07700784B2

Reaction notes

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