Sodium Hydroxide → Methyl 3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)benzoate

HRID 355373Notes

Reaction equation

HRID 355373 reaction equation
C(C([CH2:10][CH3:11])(CC)C([O-])([O-])[O-])C.[NH2:12][C:13]1[CH:14]=[C:15]([CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=1)[C:16]([O:18][CH3:19])=[O:17].[N-:27]=[N+:28]=[N-:29].[Na+].[OH-].[Na+]>C(O)(=O)C.O>[CH3:11][C:10]1[N:12]([C:13]2[CH:14]=[C:15]([CH:20]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:22]=2)[C:16]([O:18][CH3:19])=[O:17])[N:29]=[N:28][N:27]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 4026781methyl 3-amino-5-(trifluoromethyl)benzoateHCID 21875354Triethylorthoaceate

Product 1

HCID 18942151Methyl 3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)benzoateYield 57%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

Triethylorthoacetate (2.57 ml, 14 mmol) was added to a stirred, heated (75° C.) solution of methyl 3-amino-5-(trifluoromethyl)benzoate (the product of Description 1, step ii) (2.19 g, 10 mmol) in acetic acid (15 ml). The mixture was stirred at 75° C. for 45 minutes, then sodium azide (1.95 g, 30 mmol) was added in portions over 45 minutes. The mixture was stirred at 75° C. for 4 hours, cooled and poured into water (50 ml). The pH was adjusted to 7.0 with aqueous sodium hydroxide (4M) and the mixture was extracted with ethyl acetate (3×50 ml). The combined organic fractions were washed with saturated aqueous sodium hydrogen carbonate (2×50 ml) and brine (50 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate/hexane (30:70 increasing to 60:40) to give methyl 3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)benzoate as a yellow oil (1.62 g, 57%), 1H (CDCl3) δ 8.51 (1H, s), 8.36 (1H, s), 8.02 (1H, s), 4.03 (3H, s), and 2.71 (3H, s). m/z 287 (M+H+).

Workup

  1. stirringThe mixture was stirred at 75° C. for 4 hours
  2. temperaturecooled
  3. extractionthe mixture was extracted with ethyl acetate (3×50 ml)
  4. washThe combined organic fractions were washed with saturated aqueous sodium hydrogen carbonate (2×50 ml) and brine (50 ml)
  5. dry with materialdried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with ethyl acetate/hexane (30:70 increasing to 60:40)

Sources & evidence

ORD record
ord-a8140f66436d491ab4c6d33933a36986
Source dataset
uspto-grants-1998_11
Patent number
US05830892

Reaction notes

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