Sodium Azide → 5-Chloromethyl-1-(4-methoxy-benzyl)-1H-tetrazole

HRID 1264393Notes

Reaction equation

HRID 1264393 reaction equation
[Cl:1][CH2:2][C:3](OCC)(OCC)OCC.[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][CH:16]=1.[N-:23]=[N+:24]=[N-:25].[Na+].C([O-])(O)=O.[Na+].CCOC(C)=O>C(O)(=O)C>[Cl:1][CH2:2][C:3]1[N:20]([CH2:19][C:18]2[CH:21]=[CH:22][C:15]([O:14][CH3:13])=[CH:16][CH:17]=2)[N:25]=[N:24][N:23]=1

Participants

6

Reactant 4

HCID 33557Sodium AzideHCID 754524-MethoxybenzylamineHCID 3059222-Chloro-1,1,1-triethoxyethaneHCID 86584982Sodium bicarbonate ethyl acetate

Product 1

HCID 109990845-Chloromethyl-1-(4-methoxy-benzyl)-1H-tetrazoleYield 47%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 9.55 g (48.6 mmol) 2-chloro-1,1,1-triethoxyethane and 3.9 ml (30 mmol) 4-methoxybenzylamine were heated at 40° C. for 15 min. Then a solution of 2.92 g (45 mmol) sodium azide in 60 ml acetic acid was added at RT and heated at 60° C. over night, 20h at 80° C. and 1h at 100° C. The reaction was neutralized with aqueous and solid NaHCO3/EtOAc (3×), washed with aqueous 10% NaCl. The organic phase was dried over Na2SO4, evaporated and purified by flash-chromatography on silicagel (hexane/EtOAc 1:1) to give 3.36 g (47%) 5-Chloromethyl-1-(4-methoxy-benzyl)-1H-tetrazole, MS: 238 (M). [Y. Satoh, S. De Lombaert, N. Marcopulos, J. Moliterni, M. Moskal, J. Tan, E. Wallace, Synthesis of tetrazole analogs of alpha-amino acids by alkylation of a Schiff base of alpha-aminomethyltetrazole. Tetrahedron Lett. (1998), 39(21), 3367-3370].

Workup

  1. customat 80° C.
  2. customat 100° C
  3. washwashed with aqueous 10% NaCl
  4. dry with materialThe organic phase was dried over Na2SO4
  5. customevaporated
  6. custompurified by flash-chromatography on silicagel (hexane/EtOAc 1:1)

Sources & evidence

ORD record
ord-966e68d856934cee989bf3220aa8b77e
Source dataset
uspto-grants-2003_04
Patent number
US06541638B2

Reaction notes

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