N,N,N',N'-Tetramethylethylenediamine → (RS)-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]-(2-methylphenyl)methanol

HRID 1004322Notes

Reaction equation

HRID 1004322 reaction equation
[CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]([CH2:7][N:8]2[CH:12]=[N:11][N:10]=[N:9]2)=[CH:5][CH:4]=1.CN(C)CCN(C)C.C([Li])CCC.[C:28]1([CH3:36])[C:29]([CH:34]=[O:35])=[CH:30][CH:31]=[CH:32][CH:33]=1>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:12]([CH:34]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[CH3:36])[OH:35])=[N:11][N:10]=[N:9]2)=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 107222-MethylbenzaldehydeHCID 109978051-((4-methoxyphenyl)methyl)-1H-1,2,3,4-tetrazoleHCID 178418339Butyllithium

Product 1

HCID 23294867(RS)-[1-(4-Methoxybenzyl)-1H-tetrazol-5-yl]-(2-methylphenyl)methanolYield 85.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-85 °C

Procedure

A stirred solution of 1-(4-methoxybenzyl)tetrazole (7.04 g, Tetrahedron Letters, 1995, p1759-1762) in a mixture of dry tetrahydrofuran (120 ml) and N,N,N',N',-tetramethylethylenediamine (12 ml) under a nitrogen atmosphere at -85° C. was treated dropwise with n-butyl lithium (18 ml, 2.5M solution in hexanes) over 10 minutes. After stirring at -85° C. for an additional 5 minutes a solution of o-tolualdehyde (4.45 g) in dry tetrahydrofuran (20 ml) was added dropwise over 10 minutes. The reaction mixture was stirred at -85° C. for 30 minutes, allowed to warm to room temperature, then quenched with saturated ammonium chloride solution (50 ml). The organic phase was separated and the aqueous phase extracted three times with ethyl acetate (100 ml). The combined organic phases were dried over magnesium sulphate and evaporated. The residue was purified by flash chromatography on silica eluting initially with a mixture of ethyl acetate and pentane (1:1, v/v) then with a mixture of ethyl acetate and pentane (66:34, v/v). Fractions homogenous in the required product were combined and evaporated affording the title compound (9.8 g) as a white solid, m.p. 90-92° C. [Elemental analysis:- C,65.91, H,5.9, N,18.1%. Calculated:- C,65.79, H,5.85, N,18.05%].

Workup

  1. additionwas added dropwise over 10 minutes
  2. temperatureto warm to room temperature
  3. customquenched with saturated ammonium chloride solution (50 ml)
  4. customThe organic phase was separated
  5. extractionthe aqueous phase extracted three times with ethyl acetate (100 ml)
  6. dry with materialThe combined organic phases were dried over magnesium sulphate
  7. customevaporated
  8. customThe residue was purified by flash chromatography on silica eluting initially with a mixture of ethyl acetate and pentane (1:1
  9. additionv/v) then with a mixture of ethyl acetate and pentane (66:34
  10. customevaporated

Sources & evidence

ORD record
ord-291fefb55c8645b98983099d489f17b8
Source dataset
uspto-grants-2000_04
Patent number
US06048893

Reaction notes

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