Tetrahydrofuran → 5-(4'-diethoxymethyl-biphenyl-2-yl)-2-(tetrahydropyran-2-yl)-2H-tetrazole

HRID 644922Notes

Reaction equation

HRID 644922 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]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[N:17]=1.ClC1C=CC=CC=1C1N(C2CCCCO2)N=NN=1.[CH2:42]([O:44][CH:45]([O:54][CH2:55][CH3:56])[C:46]1[CH:51]=[CH:50][C:49]([Mg]Br)=[CH:48][CH:47]=1)[CH3:43]>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-]>[CH2:55]([O:54][CH:45]([O:44][CH2:42][CH3:43])[C:46]1[CH:51]=[CH:50][C:49]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]2[N:14]=[N:15][N:16]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[N:17]=2)=[CH:48][CH:47]=1)[CH3:56]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 675464055-(2-chlorophenyl)-1-(tetrahydropyran-2-yl)-1H-tetrazoleHCID 675468845-(2-Chlorophenyl)-2-(oxan-2-yl)-2H-tetrazoleHCID 178470948HCID 178470948, compound

Product 1

HCID 586182215-(4'-diethoxymethyl-biphenyl-2-yl)-2-(tetrahydropyran-2-yl)-2H-tetrazole

Reagents, catalysts & solvents 3

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

Conditions

Temperature
0 °C

Procedure

In another flask, dichloro[1,3bis(diphenylphosphino)propane]nickel(II) (0.027 g; 0.05 mmol) is suspended in tert-butyl methyl ether (3.8 mL) and cooled to about 0° C. before a 0.5 M solution of zinc chloride in tetrahydrofuran (0.50 mL; 0.25 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 (1.32 g; 5.0 mmol) in tert-butyl methyl ether (1.3 mL) are added. To the vigorously stirred resulting suspension is added at about 0° C. 13 mL of the above 0.46 M 4-(diethoxymethyl)phenylmagnesium bromide solution (6.0 mmol) over one hour. The resulting black-yellow solution is stirred at about 0° C. for 5 hours, allowed to warm up and further stirred at room temperature for 19 hours. The mixture is cooled to about 0° C. and quenched with a 7.5% solution of ammonium chloride in water (10 mL). The aqueous phase is separated and extracted with ethyl acetate (25 mL). The combined organic phases are washed with water (10 mL), a 7.5% solution of sodium carbonate in water (10 mL) and a 10% solution of sodium chloride in water (10 mL). The combined organic phases are evaporated in vacuo. A solution of the resulting brown-yellow oil in a small amount of ethyl acetate is filtered and evaporated. The resulting oil (2.68 g) is purified by column chromatography on silica gel eluting with a 1:4 mixture of ethyl acetate and hexane (in the presence of 0.2 volume-% of triethylamine) to afford the main isomer (N2-isomer) 5-(4′-diethoxymethyl-biphenyl-2-yl)-2-(tetrahydro-pyran-2-yl)-2H-tetrazole as a colorless oil.

Workup

  1. additionare added
  2. customresulting suspension
  3. additionis added at about 0° C
  4. stirringThe resulting black-yellow solution is stirred at about 0° C. for 5 hours
  5. temperatureto warm up
  6. stirringfurther stirred at room temperature for 19 hours
  7. customquenched with a 7.5% solution of ammonium chloride in water (10 mL)
  8. customThe aqueous phase is separated
  9. extractionextracted with ethyl acetate (25 mL)
  10. washThe combined organic phases are washed with water (10 mL)
  11. customThe combined organic phases are evaporated in vacuo
  12. filtrationA solution of the resulting brown-yellow oil in a small amount of ethyl acetate is filtered
  13. customevaporated
  14. customThe resulting oil (2.68 g) is purified by column chromatography on silica gel eluting with a 1:4 mixture of ethyl acetate and hexane (in the presence of 0.2 volume-% of triethylamine)

Sources & evidence

ORD record
ord-2a52cf4d08e34b319bdea9552d2006be
Source dataset
uspto-grants-2010_04
Patent number
US07700784B2

Reaction notes

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