2-(1-Methoxy-1-methylethyl)-5-methyl-2h-tetrazole → 1-{4-[(4-Tert-butylcyclohexylamino)methyl]phenyl}-2-[2-(1-methoxy-1-methylethyl)-2h-tetrazol-5-yl]ethanone

HRID 480380Notes

Reaction equation

HRID 480380 reaction equation
[CH3:1][O:2][C:3]([N:6]1[N:10]=[N:9][C:8]([CH3:11])=[N:7]1)([CH3:5])[CH3:4].C([Li])CCC.CON(C)[C:20](=[O:39])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][NH:28][C@H:29]2[CH2:34][CH2:33][C@H:32]([C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:31][CH2:30]2)=[CH:23][CH:22]=1>C1COCC1>[C:35]([CH:32]1[CH2:31][CH2:30][CH:29]([NH:28][CH2:27][C:24]2[CH:25]=[CH:26][C:21]([C:20](=[O:39])[CH2:11][C:8]3[N:9]=[N:10][N:6]([C:3]([O:2][CH3:1])([CH3:5])[CH3:4])[N:7]=3)=[CH:22][CH:23]=2)[CH2:34][CH2:33]1)([CH3:38])([CH3:36])[CH3:37]

Participants

5

Reactant 3

HCID 187689122-(1-Methoxy-1-methylethyl)-5-methyl-2h-tetrazoleHCID 178418339ButyllithiumHCID 178502668HCID 178502668, compound

Product 1

HCID 187688831-{4-[(4-Tert-butylcyclohexylamino)methyl]phenyl}-2-[2-(1-methoxy-1-methylethyl)-2h-tetrazol-5-yl]ethanoneYield 101.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-(1-methoxy-1-methylethyl)-5-methyl-2H-tetrazole (893 mg, 5.7 mmol) in THF (10 ml) cooled to −78° C. on a dry-ice-acetone bath was added dropwise a solution of n-butyl lithium in hexanes (3.6 ml, 1.6 M, 5.7 mmol). The mixture was stirred at −78° C. for 30 min, and at 0° C. for an additional 30 min, then recooled to −78° C. This solution was then slowly transferred (by cannulation) to a solution of N-methoxy-N-methyl-trans-4-{[4-tert-butylcyclohexylamino]methyl}benzamide (760 mg, 2.3 mmol) in THF (15 ml) maintained at −78° C. The reaction mixture was stirred for 30 min at −78° C. and then quenched by the addition of methanol (2 ml). Solvent was removed by rotary evaporation, and the residue was dissolved in ethyl acetate (100 ml). The organic phase was washed once with saturated aqueous sodium hydrogen carbonate (100 ml); dried over anhydrous sodium sulphate and taken to dryness by rotary evaporation to leave 1.0 g (100%) of the title material as an clear oil.

Workup

  1. waitat 0° C. for an additional 30 min
  2. customrecooled to −78° C
  3. temperaturemaintained at −78° C
  4. stirringThe reaction mixture was stirred for 30 min at −78° C.
  5. customquenched by the addition of methanol (2 ml)
  6. customSolvent was removed by rotary evaporation
  7. dissolutionthe residue was dissolved in ethyl acetate (100 ml)
  8. washThe organic phase was washed once with saturated aqueous sodium hydrogen carbonate (100 ml)
  9. dry with materialdried over anhydrous sodium sulphate
  10. customtaken to dryness by rotary evaporation

Sources & evidence

ORD record
ord-135087e208724b7997ca695e4ae3404e
Source dataset
uspto-grants-2003_11
Patent number
US06649641B2

Reaction notes

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