Sodium hydride → 5-(3-Cyclohexyl-propoxy)-1-(4-nitro-phenyl)-1H-tetrazole

HRID 1004652Notes

Reaction equation

HRID 1004652 reaction equation
[CH:1]1([CH2:7][CH2:8][CH2:9][OH:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:14]1[N:18]([C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=2)[N:17]=[N:16][N:15]=1>O1CCCC1>[CH:1]1([CH2:7][CH2:8][CH2:9][O:10][C:14]2[N:18]([C:19]3[CH:20]=[CH:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=3)[N:17]=[N:16][N:15]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 707633-Cyclohexyl-1-propanolHCID 15852121HCID 15852121, compound

Product 1

HCID 224717005-(3-Cyclohexyl-propoxy)-1-(4-nitro-phenyl)-1H-tetrazoleYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Cyclohexylpropyl alcohol (237 mL, 1.56 mol) was added to a suspension of NaH (66.0 g, 1.65 mol) in tetrahydrofuran (1.40 L). A solution of 5-Chloro-1-(4-nitro-phenyl)-1H-tetrazole (320 g, 1.42 mol) in tetrahydrofuran (900 mL) was added dropwise over 1.5 hours. The reaction was allowed to cool to room temperature and stirred overnight. The mixture was concentrated in vacuo to a solid. The solid was dissolved in ethyl acetate, washed with saturated aqueous sodium chloride solution (2×), dried (Na2SO4), and filtered through silica gel (700 g). The red filtrate was concentrated in vacuo until product began to precipitate from solution. Hexane was added and the slurry filtered to provide a tan solid (320 g, 64%). Mp 82-88° C. (dec); 1H NMR (CDCl3, 300 MHz) δ 8.43 (d, 9.2 Hz, 2 H), 8.04 (d, 9.2 Hz, 2 H), 4.70 (t, 7.0 Hz, 2 H), 1.96 (m, 2 H), 1.75-1.64 (m, 5 H), 1.39-1.13 (m, 6 H), 0.97-0.87 (m, 2 H); MS (CI) m/z 332 (MH+); Anal. calcd for C16H21N5O3 : C, 57.99; H, 6.39; N, 21.13. Found: C, 57.80; H, 6.35; N, 21.02; Rf =0.43 (N).

Workup

  1. concentrationThe mixture was concentrated in vacuo to a solid
  2. dissolutionThe solid was dissolved in ethyl acetate
  3. washwashed with saturated aqueous sodium chloride solution (2×)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered through silica gel (700 g)
  6. concentrationThe red filtrate was concentrated in vacuo until product
  7. customto precipitate from solution
  8. additionHexane was added
  9. filtrationthe slurry filtered

Sources & evidence

ORD record
ord-4dd0786e892045d4b7824e43f875e8c5
Source dataset
uspto-grants-2000_04
Patent number
US06051586

Reaction notes

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