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

HRID 644922ノート

反応式

HRID 644922 の反応式
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]

参加物

8

反応物 4

HCID 8028TetrahydrofuranHCID 675464055-(2-chlorophenyl)-1-(tetrahydropyran-2-yl)-1H-tetrazoleHCID 675468845-(2-Chlorophenyl)-2-(oxan-2-yl)-2H-tetrazoleHCID 178470948HCID 178470948、化合物

生成物 1

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

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 178418745HCID 178418745、化合物触媒HCID 15413tert-Butyl methyl ether溶媒2 回

反応条件

温度
0 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-2a52cf4d08e34b319bdea9552d2006be
出典データセット
uspto-grants-2010_04
特許番号
US07700784B2

反応ノート

読み込み中…