Tetrahydrofuran → 5-(4'-[1,3]dioxan-2-yl-biphenyl-2-yl)-2-(1-methyl-1-phenylethyl)-2H-tetrazole

HRID 644921Notes

Reaction equation

HRID 644921 reaction equation
O1CCCC1.Cl[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]1[N:14]=[N:15][N:16]([C:18]([CH3:26])([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH3:19])[N:17]=1.[O:27]1[CH2:32][CH2:31][CH2:30][O:29][CH:28]1[C:33]1[CH:38]=[CH:37][C:36]([Mg]Br)=[CH:35][CH:34]=1>COC(C)(C)C.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-]>[O:27]1[CH2:32][CH2:31][CH2:30][O:29][CH:28]1[C:33]1[CH:34]=[CH:35][C:36]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]2[N:14]=[N:15][N:16]([C:18]([CH3:26])([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])[N:17]=2)=[CH:37][CH:38]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 542959905-(2-chloro-phenyl)-2-(1-methyl-1-phenyl-ethyl)-2H-tetrazoleHCID 178419619HCID 178419619, compound

Product 1

HCID 113393185-(4'-[1,3]dioxan-2-yl-biphenyl-2-yl)-2-(1-methyl-1-phenylethyl)-2H-tetrazole

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418745HCID 178418745, compoundCatalystHCID 15413tert-Butyl methyl etherSolvent2×

Conditions

Temperature
0 °C

Procedure

In another flask, dichloro[1,3-bis(diphenylphosphino)propane]nickel(II) (0.022 g; 0.04 mmol) is suspended in tert-butyl methyl ether (3 mL) and cooled to about 0° C. before a 0.5 M solution of zinc chloride in tetrahydrofuran (0.40 mL; 0.20 mmol) and a solution of 5-(2-chloro-phenyl)-2-(1-methyl-1-phenyl-ethyl )-2H-tetrazole (1.20 g; 4.0 mmol) in tert-butyl methyl ether (1.2 mL) are added. To the vigorously stirred resulting suspension is added at about 0° C. 9.6 mL of the above 0.5 M 4-([1,3]dioxan-2-yl)phenylmagnesium bromide solution (4.8 mmol) over one hour. The resulting dark brown solution is allowed to warm up and further stirred at room temperature for 20 hours. The mixture is cooled to about 0° C., quenched with 10 mL of a 3.8% solution of ammonium chloride in water and diluted with ethyl acetate (25 mL). The aqueous phase is separated and extracted with ethyl acetate (25 mL). The combined organic phases are washed with a 0.5 M solution of sodium hydroxide in water (10 mL) and with a 10% solution of sodium chloride in water (10 mL). The combined organic phases are evaporated in vacuo. A solution of the resulting pale green solid in a small amount of ethyl acetate is filtered and evaporated. The resulting pale green solid is purified by column chromatography on silica gel eluting with a 1:10 mixture of tert-butyl methyl ether and toluene to afford 5-(4′-[1,3]dioxan-2-yl-biphenyl-2-yl)-2-(1-methyl-1-phenyl-ethyl)-2H-tetrazole as colorless crystals.

Workup

  1. customresulting suspension
  2. additionis added at about 0° C
  3. temperatureto warm up
  4. stirringfurther stirred at room temperature for 20 hours
  5. customquenched with 10 mL of a 3.8% solution of ammonium chloride in water
  6. additiondiluted with ethyl acetate (25 mL)
  7. customThe aqueous phase is separated
  8. extractionextracted with ethyl acetate (25 mL)
  9. washThe combined organic phases are washed with a 0.5 M solution of sodium hydroxide in water (10 mL) and with a 10% solution of sodium chloride in water (10 mL)
  10. customThe combined organic phases are evaporated in vacuo
  11. filtrationA solution of the resulting pale green solid in a small amount of ethyl acetate is filtered
  12. customevaporated
  13. customThe resulting pale green solid is purified by column chromatography on silica gel eluting with a 1:10 mixture of tert-butyl methyl ether and toluene

Sources & evidence

ORD record
ord-dd75fdb0fda149e1a4196ab57f9fdcf4
Source dataset
uspto-grants-2010_04
Patent number
US07700784B2

Reaction notes

Loading…